Fused-ring compounds and use thereof as drugs

Abstract

The present invention provides a fused ring compound of the following formula [I] 1

Description

[0001] This application is a divisional of copending U.S. patent application Ser. No. 09/939,374, filed Aug. 24, 2001, which is a continuation-in-part of PCT/JP00/09181 filed on Dec. 22, 2000.

TECHNICAL FIELD

[0002] The present invention relates to a novel fused ring compound and a pharmaceutically acceptable salt thereof useful as a therapeutic agent for hepatitis C, and to an intermediate compound for the synthesis thereof. The present invention also relates to a novel use of a certain fused ring compound or a pharmaceutically acceptable salt thereof as a therapeutic agent for hepatitis C. More particularly, the present invention relates to a therapeutic agent for hepatitis C, which contains a novel fused ring compound or a Pharmaceutically acceptable salt thereof, which is effective for the prophylaxis or treatment of hepatitis C and which shows anti-hepatitis C virus (HCV) activity, particularly anti-HCV activity based on an RNA-dependent RNA polymerase inhibitory activity.

BACKGROUND ART

[0003] In 1989, a main causative virus of non-A non-B posttransfusion hepatitis was found and named hepatitis C virus (HCV). Since then, several types of hepatitis viruses have been found besides type A, type B and type C, wherein hepatitis caused by HCV is called hepatitis C.

[0004] The patients infected with HCV are considered to involve several percent of the world population, and the infection with HCV characteristically becomes chronic.

[0005] HCV is an envelope RNA virus, wherein the genome is a single strand plus-strand RNA, and belongs to the genus Hepacivirus of Flavivirus (from The International Committee on Taxonomy of Viruses, International Union of Microbiological Societies). Of the same hepatitis viruses, for example, hepatitis B virus (HBV), which is a DNA virus, is eliminated by the immune system and the infection with this virus ends in an acute infection except for neonates and infants having yet immature immunological competence. In contrast, HCV somehow avoids the immune system of the host due to an unknown mechanism. Once infected with this virus, even an adult having a mature immune system frequently develops persistent infection.

[0006] When chronic hepatitis is associated with the persistent infection with HCV, it advances to cirrhosis or hepatic cancer in a high rate. Enucleation of tumor by operation does not help much, because the patient often develops recurrent hepatic cancer due to the sequela inflammation in non-cancerous parts.

[0007] Thus, an effective therapeutic method of hepatitis C is desired. Apart from the symptomatic therapy to suppress inflammation with an anti-inflammatory agent, the development of a therapeutic agent that reduces HCV to a low level free from inflammation and that eradicates HCV has been strongly demanded.

[0008] At present, a treatment with interferon is the only effective method known for the eradication of HCV. However, interferon can eradicate the virus only in about one-third of the patient population. For the rest of the patients, it has no effect or provides only a temporary effect. Therefore, an anti-HCV drug to be used in the place of or concurrently with interferon is awaited in great expectation.

[0009] In recent years, Ribavirin (1-&bgr;-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) has become commercially available as a therapeutic agent for hepatitis C, which is to be used concurrently with interferon. It enhances the efficacy of interferon but only to a low efficacy rate, and a different novel therapeutic agent for hepatitis C is desired.

[0010] Also, an attempt has been made to potentiate the immunocompetence of the patient with an interferon agonist, an interleukin-12 agonist and the like, thereby to eradicate the virus, but an effective pharmaceutical agent has not been found yet.

[0011] In addition, the inhibition of HCV growth, wherein HCV-specific protein is targeted, has been drawing attention these days.

[0012] The gene of HCV encodes a protein such as serine protease, RNA helicase, RNA-dependent RNA polymerase and the like. These proteins function as a specific protein essential for the growth of HCV.

[0013] One of the specific proteins, RNA-dependent RNA polymerase (hereinafter to be also briefly referred to as an HCV polymerase), is an enzyme essential for the growth of the virus. The gene replication of HCV having a plus-strand RNA gene is considered to involve synthesis of a complementary minus-strand RNA by the use of the plus-strand RNA as a template, and, using the obtained minus-strand RNA as a template, amplifying the plus-strand RNA. The portion called NS5B of a protein precursor, that HCV codes for, has been found to show an RNA-dependent RNA polymerase activity (EMBO J., 15, 12-22, 1996), and is considered to play a central role in the HCV gene replication.

[0014] Therefore, an HCV polymerase inhibitor can be a target in the development of an anti-HCV drug, and the development thereof is eagerly awaited. However, an effective HCV polymerase inhibitor has not been developed yet, like in other attempts to develop an anti-HCV drug based on other action mechanisms. As the situation stands, no pharmaceutical agent can treat hepatitis C satisfactorily.

[0015] The following discloses known compounds relatively similar to the compound of the present invention.

[0016] A known therapeutic agent for hepatitis C having a benzimidazole skeleton is disclosed in WO97/36866, Japanese Patent Application under PCT laid-open under kohyo No. 2000-511899 (EP906097) and WO99/51619.

[0017] WO97/36866 discloses the following compound D and the like, and HCV helicase inhibitory activity of the compounds.

[0018] Japanese Patent Application under PCT laid-open under kohyo No. 2000-511899 (EP906097) discloses the following compound E and the like, and WO99/51619 discloses the following compound F and the like, in both of which a possibility of these compounds being effective as an HCV inhibitor is mentioned.

[0019] However, these publications do not include the compound disclosed in the present specification, or a disclosure suggestive thereof. 2

[0020] A known anti-hepatitis virus agent having a benzimidazole skeleton is disclosed in Japanese Patent Application under PCT laid-open under kohyo No. 2000-503017 (WO97/25316) and Japanese Patent Application under PCT laid-open under kohyo No. 10-505092 (WO96/7646).

[0021] WO97/25316 discloses the following compound A and the like, wherein the use thereof is for a treatment of viral infection. The target virus is a DNA virus such as hepatitis B virus and the like. However, this publication does not include the compound disclosed in the present specification or a description regarding or suggestive of HCV.

[0022] Japanese Patent Application under PCT laid-open under kohyo No. 10-505092 discloses the following compound B and the like, wherein the use thereof is for a treatment of viral infection. The target virus is a DNA virus such as herpesvirus and hepatitis B virus. However, this publication does not include the compound disclosed in the present specification or a description regarding or suggestive of HCV. 3

[0023] The benzimidazole derivatives having an antiviral activity have been disclosed in JP-A-3-31264, U.S. Pat. Nos. 3,644,382 and 3,778,504. In addition, WO98/37072 discloses, as a production inhibitor of tumor necrosis factor (TNF) and cyclic AMP, a benzimidazole derivative for the use as an anti-human immunodeficiency virus (HIV) agent and an anti-inflammation agent. WO98/05327 discloses, as a reverse transcriptase inhibitor, a benzimidazole derivative for the use as an anti-HIV agent. J. Med. Chem. (13(4), 697-704, 1970) discloses, as a neuraminidase inhibitor, a benzimidazole derivative for the use as an anti-influenza virus agent.

[0024] However, none of these publications includes the compound of the present invention or a description regarding or suggestive of an anti-HCV effect.

[0025] Known benzimidazole derivatives having a pharmaceutical use other than as an antiviral agent are disclosed in JP-A-8-501318 (U.S. Pat. No. 5,814,651) and JP-A-8-134073 (U.S. Pat. No. 5,563,143). These publications disclose the following compound C and the like as a catechol diether compound, and the use thereof as an anti-inflammation agent. However, neither of the publications includes the compound of the present invention, and as the action mechanism, the former discloses phosphodiesterase IV and the latter discloses TNF. These publications do not include a description regarding or suggestive of an anti-HCV effect.

[0026] Japanese Patent Application under PCT laid-open under kohyo No. 2000-159749 (EP882718) discloses the following compound G and the like, and the use thereof for the treatment of bronchitis, glomerulonephritis and the like. However, this publication does not include the compound of the present invention, but discloses only a phosphodiesterase IV inhibitory and hypoglycemic action. This publication does not include a description regarding or suggestive of an anti-HCV effect.

[0027] U.S. Pat. No. 6,211,177 discloses the following compound H and the like with their use as antitumor agents. However, this publication does not encompass the compound of the present invention, and does not disclose or suggest an anti-HCV effect. 4

[0028] WO98/50029, WO98/50030 and WO98/50031 disclose benzimidazole derivatives as an antitumor agent having a protein isoprenyl transferase action. While this publication discloses a wide scope of the claims, at least it does not include a compound analogous to the compound of the present invention or a description regarding or suggestive of an anti-HCV effect.

[0029] JP-A-8-109169 (EP694535) discloses the application of a tachykinin receptor antagonist to treat an inflammatory disease, and WO96/35713 discloses the application thereof as a growth hormone release promoter to treat a growth hormone-related disease such as osteoporosis and the like. However, none of these publications includes a description regarding or suggestive of an anti-HCV effect.

[0030] WO2001/21634 discloses the following compound I in a chemical library. However, this publication does not encompass the compound of the present invention. While it discloses an antimicrobial activity of certain compounds, this publication does not teach or suggest an anti-HCV effect. 5

[0031] JP-A-53-14735 discloses a benzimidazole derivative as a brightener besides its pharmaceutical use, but this publication does not include the compound of the present invention.

SUMMARY OF THE INVENTION

[0032] Based on the findings from the preceding studies, it has been elucidated that a pharmaceutical agent having an anti-HCV activity is effective for the prophylaxis and treatment of hepatitis C, and particularly an anti-HCV agent having an inhibitory activity on RNA-dependent RNA polymerase of HCV can be a prophylactic and therapeutic agent effective against hepatitis C and a prophylactic and therapeutic agent for the disease caused by hepatitis C.

[0033] Accordingly, the present invention provides a pharmaceutical agent having an anti-HCV activity, particularly a pharmaceutical agent having an RNA-dependent RNA polymerase inhibitory activity.

[0034] The present inventors have made an in-depth study of compounds having an anti-HCV activity, particularly RNA-dependent RNA polymerase inhibitory activity, and completed the present invention.

[0035] Thus, the present invention provides the following (1) to (117).

[0036] (1) A therapeutic agent for hepatitis C, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient: 6

[0037] wherein

[0038] a broken line is a single bond or a double bond,

[0039] G1 is C(—R1) or a nitrogen atom,

[0040] G2 is C(—R2) or a nitrogen atom,

[0041] G3 is C(—R3) or a nitrogen atom,

[0042] G4 is C(—R4) or a nitrogen atom,

[0043] G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,

[0044] G7 is C(—R7), an oxygen atom, a sulfur atom, or a nitrogen atom optionally substituted by R8,

[0045] wherein R1, R2, R3 and R4 are each independently,

[0046] (1) hydrogen atom,

[0047] (2) C1-6 alkanoyl,

[0048] (3) carboxyl,

[0049] (4) cyano,

[0050] (5) nitro,

[0051] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,

[0052] group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

[0053] (7) —COORa1

[0054] wherein Ra1 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B or glucuronic acid residue,

[0055] group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,

[0056] (8) —CONRa2Ra3

[0057] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

[0058] (9) —C(═NRa4)NH2

[0059] wherein Ra4 is hydrogen atom or hydroxyl group,

[0060] (10) —NHRa5

[0061] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

[0062] (11) —ORa6

[0063] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl(as defined above),

[0064] (12) —SO2Ra7

[0065] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,

[0066] (13) —P(═O)(ORa31)2

[0067] wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0068] (14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

[0069] R7 and R8 are each hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

[0070] ring Cy is

[0071] (1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy,

[0072] (2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or

[0073] (3) 7

[0074] wherein u and v are each independently an integer of 1 to 3,

[0075] ring A is

[0076] (1) C6-14 aryl,

[0077] (2) C3-8 cycloalkyl,

[0078] (3) C3-8 cycloalkenyl or

[0079] (4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0080] R5 and R6 are each independently

[0081] (1) hydrogen atom,

[0082] (2) halogen atom,

[0083] (3) optionally substituted C1-6 alkyl (as defined above) or

[0084] (4) —ORa8

[0085] wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and

[0086] X is

[0087] (1) hydrogen atom,

[0088] (2) halogen atom,

[0089] (3) cyano,

[0090] (4) nitro,

[0091] (5) amino, C1-6 alkanoylamino,

[0092] (6) C1-6 alkylsulfonyl,

[0093] (7) optionally substituted C1-6 alkyl (as defined above),

[0094] (8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

[0095] (9) —COORa9

[0096] wherein Ra9 is hydrogen atom or C1-6 alkyl,

[0097] (10) —CONH—(CH2)1—Ra10

[0098] wherein Ra10 is optionally substituted C1-6 alkyl (as defined above), C1-6 alkoxycarbonyl or C1-6 alkanoylamino and 1 is 0 or an integer of 1 to 6,

[0099] (11) —ORa11

[0100] wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above) or

[0101] (12) 8

[0102]  wherein

[0103] ring B is

[0104] (1′) C6-14 aryl,

[0105] (2′) C3-8 cycloalkyl or

[0106] (3′) heterocyclic group (as defined above),

[0107] each Z is independently

[0108] (1′) a group selected from the following group D,

[0109] (2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0110] (3′) C3-8 cycloalkyl optionally substituted by 1 to substituent(s) selected from the following group D,

[0111] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0112] (5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0113] wherein the heterocyclic group has 1 to 4 hetero atom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or

[0114] (6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0115] wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, as defined above,

[0116] group D:

[0117] (a) hydrogen atom,

[0118] (b) halogen atom,

[0119] (c) cyano,

[0120] (d) nitro,

[0121] (e) optionally substituted C1-6 alkyl (as defined above),

[0122] (f) —(CH2)t—CORa18, (hereinafter each t means independently 0 or an integer of 1 to 6),

[0123] wherein Ra18 is

[0124] (1″) optionally substituted C1-6 alkyl (as defined above),

[0125] (2″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0126] (3″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0127] (g) —(CH2)t—COORa19

[0128] wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0129] (h) —(CH2)t—CONRa27Ra28

[0130] wherein Ra27 and Ra28 are each independently,

[0131] (1″) hydrogen atom,

[0132] (2″) optionally substituted C1-6 alkyl (as defined above),

[0133] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0134] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0135] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0136] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0137] wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,

[0138] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0139] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0140] (9″) hydroxyl group or

[0141] (10″) C1-6 alkoxy,

[0142] (i) —(CH2)t—C(═NRa33)NH2

[0143] wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,

[0144] (j) —(CH2)t—ORa20

[0145] wherein Ra20 is

[0146] (1″) hydrogen atom,

[0147] (2″) optionally substituted C1-6 alkyl (as defined above),

[0148] (3″) optionally substituted C2-6 alkenyl (as defined above),

[0149] (4″) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

[0150] (5″) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B,

[0151] (6″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0152] (7″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0153] (8″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0154] (9″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0155] (10″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0156] (k) —(CH2)t—O—(CH2)p—CORa21

[0157] wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,

[0158] (1) —(CH2)t—NRa22Ra23

[0159] wherein Ra22 and Ra23 are each independently

[0160] (1″) hydrogen atom,

[0161] (2″) optionally substituted C1-6 alkyl (as defined above),

[0162] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0163] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0164] (5″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0165] (6″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0166] (m) —(CH2)t—NRa29CO—Ra24

[0167] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and

[0168] Ra24 is

[0169] (1″) amino,

[0170] (2″) C1-6 alkylamino,

[0171] (3″) optionally substituted C1-6 alkyl (as defined above),

[0172] (4″) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B,

[0173] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0174] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0175] (n) —(CH2)t—NRa29SO2—Ra25

[0176] wherein Ra29 is as defined above, and Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0177] (o) —(CH2)t—S(O)q—Ra25

[0178] wherein Ra25 is as defined above, and q is 0, 1 or 2,

[0179] (p) —(CH2)t—SO2—NHRa26

[0180] wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and

[0181] (q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

[0182] w is an integer of 1 to 3, and

[0183] Y is

[0184] (1′) a single bond,

[0185] (2′) C1-6 alkylene,

[0186] (3′) C2-6 alkenylene,

[0187] (4′) —(CH2)m—O—(CH2)n—,

[0188] (hereinafter m and n are each independently 0 or an integer of 1 to 6),

[0189] (5′) —CO—,

[0190] (6′) —CO2—(CH2)n—,

[0191] (7′) —CONH—(CH2)n—NH—,

[0192] (8′) —NHCO2—,

[0193] (9′) —NHCONH—,

[0194] (10′) —O—(CH2)n—CO—,

[0195] (11′) —O—(CH2)n—O—,

[0196] (12′) —SO2—,

[0197] (13′) —(CH2)m—NRa12—(CH2)n—

[0198] wherein Ra12 is

[0199] (1″) hydrogen atom,

[0200] (2″) optionally substituted C1-6 alkyl (as defined above),

[0201] (3″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0202] (4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0203] (5″) —CORb5

[0204] wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0205] (6″) —COORb5 (Rb5 is as defined above) or

[0206] (7″) —SO2Rb5 (Rb5 is as defined above),

[0207] (14′) —NRa12CO— (Ra12 is as defined above),

[0208] (15′) —CONRa13—(CH2)n—

[0209] wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0210] (16′) —CONH—CHRa14—

[0211] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0212] (17′) —O—(CH2)m—CRa15Ra16—(CH2)n—

[0213] wherein Ra15 and Ra16 are each independently

[0214] (1″) hydrogen atom,

[0215] (2″) carboxyl,

[0216] (3″) C1-6 alkyl,

[0217] (4″) —ORb6

[0218] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

[0219] (5″) —NHRb7

[0220] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally

[0221] (6″) 9

[0222] wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,

[0223] (18′) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),

[0224] (19′) —NRa17SO2—

[0225] wherein Ra17 is hydrogen atom or C1-6 alkyl,

[0226] (20′) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2,

[0227] Ra15 and Ra16 are each as defined above), or

[0228] (21′) —(CH2)m—CRa15Ra16—(CH2)n— (Ra15 and Ra16 are each as defined above).

[0229] (2) The therapeutic agent of (1) above, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is (are) a nitrogen atom.

[0230] (3) The therapeutic agent of (2) above, wherein G2 is C(—R2) and G6 is a carbon atom.

[0231] (4) The therapeutic agent of (2) or (3) above, wherein G5 is a nitrogen atom.

[0232] (5) The therapeutic agent of (1) above, wherein, in formula [I], the moiety 10

[0233] is a fused ring selected from 11 12

[0234] (6) The therapeutic agent of (5) above, wherein, in formula [I], the moiety 13

[0235] is a fused ring selected from 14

[0236] (7) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-1] 15

[0237] wherein each symbol is as defined in (1),

[0238] or a pharmaceutically acceptable salt thereof as an active ingredient.

[0239] (8) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-2] 16

[0240] wherein each symbol is as defined in (1),

[0241] or a pharmaceutically acceptable salt thereof as an active ingredient.

[0242] (9) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-3] 17

[0243] wherein each symbol is as defined in (1),

[0244] or a pharmaceutically acceptable salt thereof as an active ingredient.

[0245] (10) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-4] 18

[0246] wherein each symbol is as defined in (1),

[0247] or a pharmaceutically acceptable salt thereof as an active ingredient.

[0248] (11) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3, —SO2Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (1)), 19

[0249] (12) The therapeutic agent of (11) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3 or —SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (1).

[0250] (13) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is —COORa1 wherein Ra1 is glucuronic acid residue.

[0251] (14) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.

[0252] (15) The therapeutic agent of any of (1) to (14) above, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino.

[0253] (16) The therapeutic agent of any of (1) to (14) above, wherein the ring Cy is 20

[0254] wherein each symbol is as defined in (1).

[0255] (17) The therapeutic agent of any of (1) to (16) above, wherein the ring A is C6-14 aryl.

[0256] (18) The therapeutic agent of any of (1) to (17) above, wherein at least one substituent optionally substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy.

[0257] (19) The therapeutic agent of any of (1) to (17) above, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— wherein each symbol is as defined in (1).

[0258] (20) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D.

[0259] (21) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by Z is a heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups: 21

[0260] wherein E1 is an oxygen atom, a sulfur atom or N(—Ra35), E2 is an oxygen atom, CH2 or N(—Ra35), E3 is an oxygen atom or a sulfur atom, wherein each Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and h′ are the same or different and each is an integer of 1 to 3.

[0261] (22) The therapeutic agent of (21) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D wherein said heterocyclic group is selected from the following groups: 22

[0262] wherein each symbol is as defined in (21).

[0263] (23) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in (1), and at least one of Ra27 and Ra28 is C1-6 alkoxy.

[0264] (24) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in (1), and Ra33 is hydroxyl group or C1-6 alkoxy.

[0265] (25) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—O—(CH2)p—CORa21 wherein each symbol is as defined in (1), and Ra21 is amino.

[0266] (26) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in (1), and Ra24 is amino or C1-6 alkylamino.

[0267] (27) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in (1), and at lease one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B.

[0268] (28) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.

[0269] (29) The therapeutic agent of (1) above, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient: 23

[0270] wherein

[0271] a broken line is a single bond or a double bond,

[0272] G1 is C(—R1) or a nitrogen atom,

[0273] G2 is C(—R2) or a nitrogen atom,

[0274] G3 is C(—R3) or a nitrogen atom,

[0275] G4 is C(—R4) or a nitrogen atom,

[0276] G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,

[0277] G7 is C(—R7), an oxygen atom, a sulfur atom, or a nitrogen atom optionally substituted by R8,

[0278] wherein R1, R2, R3 and R4 are each independently,

[0279] (1) hydrogen atom,

[0280] (2) C1-6 alkanoyl,

[0281] (3) carboxyl,

[0282] (4) cyano,

[0283] (5) nitro,

[0284] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s)selected from the following group A,

[0285] group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

[0286] (7) —COORa1

[0287] wherein Ra1 is optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B,

[0288] group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,

[0289] (8) —CONRa2Ra3

[0290] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

[0291] (9) —C(═NRa4)NH2

[0292] wherein Ra4 is hydrogen atom or hydroxyl group,

[0293] (10) —NHRa5

[0294] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

[0295] (11) —ORa6

[0296] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl(as defined above),

[0297] (12) —SO2Ra7

[0298] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino or

[0299] (13) —P(═O)(ORa31)2

[0300] wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, and

[0301] R7 and R8 are each hydrogen atom or optionally substituted C1-6 alkyl(as defined above),

[0302] ring Cy is

[0303] (1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy,

[0304] (2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or

[0305] (3) 24

[0306]  wherein u and v are each independently an integer of 1 to 3,

[0307] ring A is

[0308] (1) C6-14 aryl,

[0309] (2) C3-8 cycloalkyl,

[0310] (3) C3-8 cycloalkenyl or

[0311] (4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0312] R5 and R6 are each independently

[0313] (1) hydrogen atom,

[0314] (2) halogen atom,

[0315] (3) optionally substituted C1-6 alkyl (as defined above) or

[0316] (4) —ORa8

[0317] wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and

[0318] X is

[0319] (1) hydrogen atom,

[0320] (2) halogen atom,

[0321] (3) cyano,

[0322] (4) nitro,

[0323] (5) amino, C1-6 alkanoylamino,

[0324] (6) C1-6 alkylsulfonyl,

[0325] (7) optionally substituted C1-6 alkyl (as defined above),

[0326] (8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

[0327] (9) —COORa9

[0328] wherein Ra9 is hydrogen atom or C1-6 alkyl,

[0329] (10) —CONH—(CH2)1—Ra10

[0330] wherein Ra10 is optionally substituted C1-6 alkyl (as defined above), C1-6 alkoxycarbonyl or C1-6 alkanoylamino and 1 is 0 or an integer of 1 to 6,

[0331] (11) —ORa11

[0332] wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above) or

[0333] (12) 25

[0334]  wherein

[0335] ring B is

[0336] (1′) C6-14 aryl,

[0337] (2′) C3-8 cycloalkyl or

[0338] (3′) heterocyclic group (as defined above),

[0339] each Z is independently

[0340] (1′) a group selected from the following group D,

[0341] (2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0342] (3′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0343] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D or

[0344] (5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D

[0345] wherein the heterocyclic group has 1 to 4 hetero-atom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0346] group D:

[0347] (a) hydrogen atom,

[0348] (b) halogen atom,

[0349] (c) cyano,

[0350] (d) nitro,

[0351] (e) optionally substituted C1-6 alkyl (as defined above),

[0352] (f) —(CH2)t—CORa18,

[0353] (hereinafter each t means independently 0 or an integer of 1 to 6),

[0354] wherein Ra18 is

[0355] (1″) optionally substituted C1-6 alkyl (as defined above),

[0356] (2″) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B or

[0357] (3″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0358] (g) —(CH2)t—COORa19

[0359] wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0360] (h) —(CH2)t—CONRa27Ra28

[0361] wherein Ra27 and Ra28 are each independently,

[0362] (1″) hydrogen atom,

[0363] (2″) optionally substituted C1-6 alkyl (as defined above),

[0364] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0365] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0366] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0367] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, wherein the heterocycle C1-6 alkyl is C1-6

[0368] alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,

[0369] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0370] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0371] (i) —(CH2)t—C(═NRa33)NH2

[0372] wherein Ra33 is hydrogen atom or C1-6 alkyl,

[0373] (j) —(CH2)t—ORa20

[0374] wherein Ra20 is

[0375] (1″) hydrogen atom,

[0376] (2″) optionally substituted C1-6 alkyl (as defined above),

[0377] (3″) optionally substituted C2-6 alkenyl (as defined above),

[0378] (4″) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

[0379] (5″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0380] (6″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0381] (7″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0382] (8″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0383] (9″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0384] (10″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0385] (k) —(CH2)t—O—(CH2)p—CORa21

[0386] wherein Ra21 is C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,

[0387] (l) —(CH2)t—NRa22Ra23

[0388] wherein Ra22 and Ra23 are each independently

[0389] (1″) hydrogen atom,

[0390] (2″) optionally substituted C1-6 alkyl (as defined above),

[0391] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0392] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0393] (5″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0394] (m) —(CH2)t—NRa29CO—Ra24

[0395] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, Ra24 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0396] (n) —(CH2)t—NHSO2—Ra25

[0397] wherein Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0398] (o) —(CH2)t—S(O)q—Ra25

[0399] wherein Ra25 is as defined above, and q is 0, 1 or 2, and

[0400] (p) —(CH2)t—SO2—NHRa26

[0401] wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0402] w is an integer of 1 to 3, and

[0403] Y is

[0404] (1′) a single bond,

[0405] (2′) C1-6 alkylene,

[0406] (3′) C2-6 alkenylene,

[0407] (4′) —(CH2)m—O—(CH2)n—,

[0408] (hereinafter m and n are each independently 0 or an integer of 1 to 6),

[0409] (5′) —CO—,

[0410] (6′) —CO2—(CH2)n—,

[0411] (7′) —CONH—(CH2)n—NH—,

[0412] (8′) —NHCO2—,

[0413] (9′) —NHCONH—,

[0414] (10′) —O—(CH2)n—CO—,

[0415] (11′) —O—(CH2)n—O—,

[0416] (12′) —SO2—,

[0417] (13′) —(CH2)m—NRa12—(CH2)n—

[0418] wherein Ra12 is

[0419] (1″) hydrogen atom,

[0420] (2″) optionally substituted C1-6 alkyl (as defined above),

[0421] (3″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0422] (4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0423] (5″) —CORb5

[0424] wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0425] (6″) —COORb5 (Rb5 is as defined above) or

[0426] (7″) —SO2Rb5 (Rb5 is as defined above),

[0427] (14″) NRa12CO— (Ra12 is as defined above),

[0428] (15′) —CONRa13—(CH2)n—

[0429] wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0430] (16′) —CONH—CHRa14—

[0431] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0432] (17′) —O—(CH2)m—CRa15Ra16—(CH2)n—

[0433] wherein Ra15 and Ra16 are each independently

[0434] (1″) hydrogen atom,

[0435] (2″) carboxyl,

[0436] (3″) C1-6 alkyl,

[0437] (4″) —ORb6

[0438] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

[0439] (5″) —NHRb7

[0440] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally

[0441] (6″) 26

[0442]  wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,

[0443] (18′) —(CH2)n—NRa12—CHRa15—(Ra12 and Ra15 are each as defined above),

[0444] (19′) —NRa17SO2—

[0445] wherein Ra17 is hydrogen atom or C1-6 alkyl or

[0446] (20′) —S(O)e—(CH2)mCRa15Ra16—(CH2)n— (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above).

[0447] (30) The therapeutic agent of (29) above, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is (are) a nitrogen atom.

[0448] (31) The therapeutic agent of (30) above, wherein G2 is C(—R2) and G6 is a carbon atom.

[0449] (32) The therapeutic agent of (30) or (31) above, wherein G5 is a nitrogen atom.

[0450] (33). The therapeutic agent of (29) above, wherein, in formula [I], the moiety 27

[0451] is a fused ring selected from 28 29

[0452] (34) The therapeutic agent of (33) above, wherein, in formula [I], the moiety 30

[0453] is a fused ring selected from 31

[0454] (35) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-1] 32

[0455] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof as an active ingredient.

[0456] (36) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-2] 33

[0457] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof as an active ingredient.

[0458] (37) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-3] 34

[0459] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof as an active ingredient.

[0460] (38) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-4] 35

[0461] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof as an active ingredient.

[0462] (39) The therapeutic agent of any of (29) to (38) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3 or —SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (29).

[0463] (40) The therapeutic agent of any of (29) to (39) above, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl.

[0464] (41) The therapeutic agent of any of (29) to (40) above, wherein the ring A is C6-14 aryl.

[0465] (42) A fused ring compound of the following formula [II] 36

[0466] wherein

[0467] the moiety 37

[0468]  is a fused ring selected from 38

[0469]  wherein R1, R2, R3 and R4 are each independently,

[0470] (1) hydrogen atom,

[0471] (2) C1-6 alkanoyl,

[0472] (3) carboxyl,

[0473] (4) cyano,

[0474] (5) nitro,

[0475] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,

[0476] group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

[0477] (7) —COORa1

[0478] wherein Ra1 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B or glucuronic acid residue,

[0479] group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,

[0480] (8) —CONRa2Ra3

[0481] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

[0482] (9) —C(═NRa4)NH2

[0483] wherein Ra4 is hydrogen atom or hydroxyl group,

[0484] (10) —NHRa5

[0485] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

[0486] (11) —ORa6

[0487] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above)

[0488] (12) —SO2Ra7

[0489] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,

[0490] (13) —P(═O)(ORa31)2

[0491] wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0492] (14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

[0493] R7 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

[0494] ring Cy′ is

[0495] (1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy, or

[0496] (2) 39

[0497]  wherein u and v are each independently an integer of 1 to 3,

[0498] ring A′ is a group selected from a group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,

[0499] R5′ and R6′ are each independently

[0500] (1) hydrogen atom,

[0501] (2) halogen atom,

[0502] (3) optionally substituted C1-6 alkyl (as defined above) or

[0503] (4) hydroxyl group

[0504] ring B is

[0505] (1) C6-14 aryl,

[0506] (2) C3-8 cycloalkyl or

[0507] (3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0508] each Z is independently

[0509] (1) a group selected from the following group D,

[0510] (2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0511] (3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0512] (4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0513] (5) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or

[0514] (6) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, as defined above,

[0515] group D:

[0516] (a) hydrogen atom,

[0517] (b) halogen atom,

[0518] (c) cyano,

[0519] (d) nitro,

[0520] (e) optionally substituted C1-6 alkyl (as defined above),

[0521] (f) —(CH2)t—CORa18, (hereinafter each t means independently 0 or an integer of 1 to 6),

[0522] wherein Ra18 is

[0523] (1′) optionally substituted C1-6 alkyl (as defined above),

[0524] (2′) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B or

[0525] (3′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0526] (g) —(CH2)t—COORa19

[0527] wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0528] (h) —(CH2)t—CONRa27Ra28

[0529] wherein Ra27 and Ra28 are each independently,

[0530] (1″) hydrogen atom,

[0531] (2″) optionally substituted C1-6 alkyl (as defined above),

[0532] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0533] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0534] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0535] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0536] wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,

[0537] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B.

[0538] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0539] (9″) hydroxyl group or (10″) C1-6 alkoxy,

[0540] (i) —(CH2)t—C(═NRa33)NH2

[0541] wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,

[0542] (j) —(CH2)t—ORa20

[0543] wherein Ra20 is

[0544] (1′) hydrogen atom,

[0545] (2′) optionally substituted C1-6 alkyl (as defined above),

[0546] (3′) optionally substituted C2-6 alkenyl (as defined above),

[0547] (4′) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the, above group A,

[0548] (5′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0549] (6′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0550] (7′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0551] (8′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0552] (9′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0553] (10′) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s). selected from the above group B,

[0554] (k) —(CH2)t—O—(CH2)p—CORa21

[0555] wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,

[0556] (1) —(CH2)t—NRa22Ra23

[0557] wherein Ra22 and Ra23 are each independently

[0558] (1′) hydrogen atom,

[0559] (2′) optionally substituted C1-6 alkyl (as defined above),

[0560] (3′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0561] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected-from the above group B,

[0562] (5′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0563] (6′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0564] (m) —(CH2)t—NRa29CO—Ra24

[0565] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and

[0566] Ra24 is

[0567] (1′) amino,

[0568] (2′) C1-6 alkylamino,

[0569] (3′) optionally substituted C1-6 alkyl (as defined above),

[0570] (4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0571] (5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0572] (6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0573] (n) —(CH2)t—NRa29SO2—Ra25

[0574] wherein Ra29 is as defined above, and Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0575] (o) —(CH2)t—S(O)q—Ra25

[0576] wherein Ra25 is as defined above, and q is 0, 1 or 2,

[0577] (p) —(CH2)t—SO2—NHRa26

[0578] wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and

[0579] (q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0580] w is an integer of 1 to 3, and

[0581] Y is

[0582] (1) a single bond,

[0583] (2) C1-6 alkylene,

[0584] (3) C2-6 alkenylene,

[0585] (4) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),

[0586] (5) —CO—,

[0587] (6) —CO2—(CH2)n—,

[0588] (7) —CONH—(CH2)n—NH—,

[0589] (8) —NHCO2—,

[0590] (9) —NHCONH—,

[0591] (10) —O—(CH2)n—CO—,

[0592] (11) —O—(CH2)n—O—,

[0593] (12) —SO2—,

[0594] (13) —(CH2)m—NRa12—(CH2)n—

[0595] wherein Ra12 is

[0596] (1′) hydrogen atom,

[0597] (2′) optionally substituted C1-6 alkyl (as defined above),

[0598] (3′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0599] (4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0600] (5′) —CORb5

[0601] wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0602] (6′) —COORb5 (Rb5 is as defined above) or

[0603] (7′) —SO2Rb5 (Rb5 is as defined above),

[0604] (14) —NRa12CO— (Ra12 is as defined above),

[0605] (15) —CONRa13—(CH2)n—

[0606] wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0607] (16) —CONH—CHRa14—

[0608] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0609] (17) —O—(CH2)m—CRa15Ra16—(CH2)n—

[0610] wherein Ra15 and Ra16 are each independently

[0611] (1′) hydrogen atom,

[0612] (2′) carboxyl,

[0613] (3′) C1-6 alkyl,

[0614] (4′) —ORb6

[0615] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

[0616] (5′) —NHRb7

[0617] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or

[0618] Ra15 is optionally

[0619] (6′) 40

[0620]  wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,

[0621] (18) —(CH2)n—NRa12—CHRa15—(Ra12 and Ra15 are each as defined above),

[0622] (19) —NRa17SO2—

[0623] wherein Ra17 is hydrogen atom or C1-6 alkyl,

[0624] (20) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above), or

[0625] (21) —(CH2)m—CRa15Ra16—(CH2)n— (Ra15 and Ra16 are each as defined above),

[0626] or a pharmaceutically acceptable salt thereof.

[0627] (43) The fused ring compound of (42) above, which is represented by the following formula [II-1] 41

[0628] wherein each symbol is as defined in (42),

[0629] or a pharmaceutically acceptable salt thereof.

[0630] (44) The fused ring compound of (42) above, which is represented by the following formula [II-2] 42

[0631] wherein each symbol is as defined in (42)

[0632] or a pharmaceutically acceptable salt thereof.

[0633] (45) The fused ring compound of (42) above, which is represented by the following formula [II-3] 43

[0634] wherein each symbol is as defined in. (42),

[0635] or a pharmaceutically acceptable salt thereof.

[0636] (46) The fused ring compound of (42) above, which is represented by the following formula [II-4] 44

[0637] wherein each symbol is as defined in (42),

[0638] or a pharmaceutically acceptable salt thereof.

[0639] (47) The fused ring compound of any of (42) to (46) above,

[0640] wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3, —SO2Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are As defined in (42)), 45

[0641]  or a pharmaceutically acceptable salt thereof.

[0642] (48) The fused ring compound of (47) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in (42), or a pharmaceutically acceptable salt thereof.

[0643] (49) The fused ring compound of (48) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in (42), or a pharmaceutically acceptable salt thereof.

[0644] (50) The fused-ring compound of (49) above, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.

[0645] (51) The fused ring compound of any of (42) to (46) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is glucuronic acid residue, or a pharmaceutically acceptable salt thereof.

[0646] (52) The fused ring compound of any of (42) to (46) above, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.

[0647] (53) The fused ring compound of any of (42) to (52) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.

[0648] (54) The fused ring compound of (42) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.

[0649] (55) The fused ring compound of any of (42) to (52) above, wherein the ring Cy′ is 46

[0650] wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.

[0651] (56) The fused ring compound of any of (42) to (55) above, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.

[0652] (57) The fused ring compound of (56) above, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.

[0653] (58) The fused ring compound of (57) above, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

[0654] (59) The fused ring compound of any of (42) to (58) above, wherein at least one substituent optionaly substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.

[0655] (60) The fused ring compound of any of (42) to (59) above, wherein the Y is —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.

[0656] (61) The fused ring compound of (42) above, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.

[0657] (62) The fused ring compound of (61) above, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.

[0658] (63) The fused ring compound of any of (42) to (59) above, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.

[0659] (64) The fused ring compound of any of (42) to (63) above, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

[0660] (65) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D, or a pharmaceutically acceptable salt thereof.

[0661] (66) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups: 47

[0662] wherein E1 is an oxygen atom, a sulfur atom or N(—Ra35), E2 is an oxygen atom, CH2 or N(—Ra35), E3 is an oxygen atom or a sulfur atom, wherein each Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and h′ are the same or different and each is an integer of 1 to 3, or a pharmaceutically acceptable salt thereof.

[0663] (67) The fused ring compound of (66) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups: 48

[0664] wherein each symbol is as defined in (66), or a pharmaceutically acceptable salt thereof.

[0665] (68) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in (42), and at least one of Ra27 and Ra28 is C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.

[0666] (69) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in (42), and Ra33 is hydroxyl group or C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.

[0667] (70) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—O—(CH2)p—CORa21 wherein each symbol is as defined in (42), and Ra21 is amino, or a pharmaceutically acceptable salt thereof.

[0668] (71) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in (42), and Ra24 is amino or C1-6 alkylamino, or a pharmaceutically acceptable salt thereof.

[0669] (72) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in (42), and at least one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B, or a pharmaceutically acceptable salt thereof.

[0670] (73) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.

[0671] (74) The fused ring compound of (42) above, which is represented by the following formula [II] 49

[0672] wherein

[0673] the moiety 50

[0674]  is a fused ring selected from 51

[0675]  wherein R1, R2, R3 and R4 are each independently,

[0676] (1) hydrogen atom,

[0677] (2) C1-6 alkanoyl,

[0678] (3) carboxyl,

[0679] (4) cyano,

[0680] (5) nitro,

[0681] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,

[0682] group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

[0683] (7) —COORa1

[0684] wherein Ra1 is optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B,

[0685] group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,

[0686] (8) —CONRa2Ra3

[0687] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

[0688] (9) —C(═NRa4)NH2

[0689] wherein Ra4 is hydrogen atom or hydroxyl group,

[0690] (10) —NHRa5

[0691] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

[0692] (11) —ORa6

[0693] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

[0694] (12) —SO2Ra7

[0695] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino or

[0696] (13) —P(═O)(ORa31)2

[0697] wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, and

[0698] R7 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

[0699] ring Cy′ is

[0700] (1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C,

[0701] group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy, or

[0702] (2) 52

[0703] wherein u and v are each independently an integer of 1 to 3,

[0704] ring A′ is a group selected from a group consisting of

[0705] phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,

[0706] R5′ and R6′ are each independently

[0707] (1) hydrogen atom,

[0708] (2) halogen atom,

[0709] (3) optionally substituted C1-6 alkyl (as defined above) or

[0710] (4) hydroxyl group

[0711] ring B is

[0712] (1) C6-14 aryl,

[0713] (2) C3-8 cycloalkyl or

[0714] (3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0715] each Z is independently

[0716] (1) a group selected from the following group D,

[0717] (2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0718] (3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0719] (4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D or

[0720] (5) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, group D:

[0721] (a) hydrogen atom,

[0722] (b) halogen atom,

[0723] (c) cyano,

[0724] (d) nitro,

[0725] (e) optionally substituted C1-6 alkyl (as defined above),

[0726] (f) —(CH2)t—CORa18,

[0727] (hereinafter each t means independently 0 or an integer of 1 to 6),

[0728] wherein Ra18 is

[0729] (1′) optionally substituted C1-6 alkyl (as defined above),

[0730] (2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0731] (3′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0732] (g) —(CH2)t—COORa19

[0733] wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0734] (h) —(CH2)t—CONRa27Ra28

[0735] wherein Ra27 and Ra28 are each independently,

[0736] (1″) hydrogen atom,

[0737] (2″) optionally substituted C1-6 alkyl (as defined above),

[0738] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0739] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0740] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0741] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0742] wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,

[0743] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0744] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0745] (i) —(CH2)t—C(═NRa33)NH2

[0746] wherein Ra33 is hydrogen atom or C1-6 alkyl,

[0747] (j) —(CH2)t—ORa20

[0748] wherein Ra20 is

[0749] (1′) hydrogen atom,

[0750] (2′) optionally substituted C1-6 alkyl (as defined above),

[0751] (3′) optionally substituted C2-6 alkenyl (as defined above),

[0752] (4′) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A.

[0753] (5′) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B,

[0754] (6′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0755] (7′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0756] (8′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0757] (9′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0758] (10′) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0759] (k) —(CH2)t—O—(CH2)p—CORa21

[0760] wherein Ra21 is C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group. B,

[0761] and p is 0 or an integer of 1 to 6,

[0762] (l) —(CH2)t—NRa22Ra23

[0763] wherein Ra22 and Ra23 are each independently

[0764] (1′) hydrogen atom,

[0765] (2′) optionally substituted C1-6 alkyl (as defined above),

[0766] (3′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0767] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0768] (5′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0769] (m) —(CH2)t—NRa29CO—Ra24

[0770] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, Ra24 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0771] (n) —(CH2)t—NHSO2—Ra25

[0772] wherein Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0773] (o) —(CH2)t—S(O)q—Ra25

[0774] wherein Ra24 is as defined above, and q is 0, 1 or 2, and

[0775] (p) —(CH2)t—SO2—NHRa26

[0776] wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0777] w is an integer of 1 to 3, and

[0778] Y is

[0779] (1) a single bond,

[0780] (2) C1-6 alkylene,

[0781] (3) C2-6 alkenylene,

[0782] (4) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),

[0783] (5) —CO—,

[0784] (6) —CO2—(CH2)n—,

[0785] (7) —CONH—(CH2)n—NH—,

[0786] (8) —NHCO2—,

[0787] (9) —NHCONH—,

[0788] (10) —O—(CH2)n—CO—,

[0789] (11) —O—(CH2)n—O—,

[0790] (12) —SO2—,

[0791] (13) —(CH2)m—NRa12—(CH2)n—

[0792] wherein Ra12 is

[0793] (1′) hydrogen atom,

[0794] (2′) optionally substituted C1-6 alkyl (as defined above),

[0795] (3′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0796] (4′) C6-14 aryl-optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0797] (5′) —CORb5

[0798] wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0799] (6′) —COORb5 (Rb5 is as defined above) or

[0800] (7) —SO2Rb5 (Rb5 is as defined above),

[0801] (14) —NRa12CO— (Ra12 is as defined above),

[0802] (15) —CONRa13—(CH2)n—

[0803] wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0804] (16) —CONH—CHRa14—

[0805] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0806] (17) —O—(CH2)mCRa15Ra16—(CH2)n—

[0807] wherein Ra15 and Ra16 are each independently

[0808] (1′) hydrogen atom,

[0809] (2′) carboxyl,

[0810] (3′) C1-6 alkyl,

[0811] (4′) —ORb6

[0812] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

[0813] (5) —NHRb7

[0814] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally

[0815] (6′) 53

[0816] wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,

[0817] (18) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),

[0818] (19) —NRa17SO2—

[0819] wherein Ra17 is hydrogen atom or C1-6 alkyl or

[0820] (20) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2,

[0821] Ra15 and Ra16 are each as defined above),

[0822] or a pharmaceutically acceptable salt thereof.

[0823] (75) The fused ring compound of (74) above, which is represented by the following formula [II-1] 54

[0824] wherein each symbol is as defined in (74),

[0825] or a pharmaceutically acceptable salt thereof.

[0826] (76) The fused ring compound of (74) above, which is represented by the following formula [II-2] 55

[0827] wherein each symbol is as defined in (74),

[0828] or a pharmaceutically acceptable salt thereof.

[0829] (77) The fused ring compound of (74) above, which is represented by the following formula [II-3] 56

[0830] wherein each symbol is as defined in (74),

[0831] or a pharmaceutically acceptable salt thereof.

[0832] (78) The fused ring compound of (74) above, which is represented by the following formula [II-4] 57

[0833] wherein each symbol is as defined in (74),

[0834] or a pharmaceutically acceptable salt thereof.

[0835] (79) The fused ring compound of any of (74) to (78) above,

[0836] wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in (74), or a pharmaceutically acceptable salt thereof.

[0837] (80) The fused ring compound of (79) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in (74), or a pharmaceutically acceptable salt thereof.

[0838] (81) The fused ring compound of (80) above, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.

[0839] (82) The fused ring compound of any of (74) to (81) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.

[0840] (83) The fused ring compound of (82) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.

[0841] (84) The fused ring compound of any of (74) to (83) above, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.

[0842] (85) The fused ring compound of (84) above, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.

[0843] (86) The fused ring compound of (85) above, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

[0844] (87) The fused ring compound of any of (74) to (86) above, wherein the Y is —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (wherein each symbol is as defined in (74)), or a pharmaceutically acceptable salt thereof.

[0845] (88) The fused ring compound of (87) above, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in (74)), or a pharmaceutically acceptable salt thereof.

[0846] (89) The fused ring compound of (88) above, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in (74), or a pharmaceutically acceptable salt thereof.

[0847] (90) The fused ring compound of any of (74) to (89) above, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

[0848] (91) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of

[0849] ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 1),

[0850] 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 2),

[0851] ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (Example 3),

[0852] ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 4),

[0853] ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 5),

[0854] 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 6),

[0855] ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 7),

[0856] ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 8),

[0857] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 9),

[0858] ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylate (Example 10),

[0859] 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylic acid (Example 11),

[0860] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 12),

[0861] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide (Example 13),

[0862] 2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole (Example 14),

[0863] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime (Example 15),

[0864] ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate (Example 16),

[0865] 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 17),

[0866] ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)benzimidazole-5-carboxylate,(Example 18),

[0867] ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 19),

[0868] 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 20),

[0869] ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate (Example 21),

[0870] ethyl 2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 22),

[0871] ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 23),

[0872] 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 24),

[0873] ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 25),

[0874] 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 26),

[0875] ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 27),

[0876] ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate (Example 28),

[0877] ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylate (Example 29),

[0878] 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 30),

[0879] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 31),

[0880] ethyl 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 32),

[0881] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N,N-dimethylbenzimidazole-5-carboxamide (Example 33),

[0882] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N-methoxy-N-methylbenzimidazole-5-carboxamide (Example 34),

[0883] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-(1-hydroxy-1-methylethyl)benzimidazole (Example 35),

[0884] 5-acetyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 36),

[0885] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N-(2-dimethylaminoethyl)-benzimidazole-5-carboxamide dihydrochloride (Example 37),

[0886] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-nitrobenzimidazole (Example 38),

[0887] 5-amino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole hydrochloride (Example 39),

[0888] 5-acetylamino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 40),

[0889] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-methanesulfonyl-aminobenzimidazole (Example 41),

[0890] 5-sulfamoyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 42),

[0891] 2-[4-(4-tert-butylbenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 43),

[0892] 2-[4-(4-carboxybenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 44),

[0893] 2-[4-(4-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 45),

[0894] 2-{4-[(2-chloro-5-thienyl)methoxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 46),

[0895] 1-cyclopentyl-2-[4-(4-trifluoromethylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid (Example 47),

[0896] 1-cyclopentyl-2-[4-(4-methoxybenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 48),

[0897] 1-cyclopentyl-2-[4-(4-pyridylmethoxy)phenyl]benzimidazole-5-carboxylic acid hydrochloride (Example 49),

[0898] 1-cyclopentyl-2-[4-(4-methylbenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 50),

[0899] 1-cyclopentyl-2-{4-[(3,5-dimethyl-4-isoxazolyl)methoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 51),

[0900] 1-cyclopentyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylic acid (Example 52),

[0901] [2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazol-5-yl]-carbonylaminoacetic acid (Example 53),

[0902] 2-[4-(2-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 54),

[0903] 2-[4-(3-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 55),

[0904] 2-(4-benzyloxyphenyl)-3-cyclopentylbenzimidazole-5-carboxylic acid (Example 56),

[0905] 2-[4-(benzenesulfonylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 57),

[0906] 1-cyclopentyl-2-[4-(3,5-dichlorophenylcarbonylamino)phenyl]-benzimidazole-5-carboxylic acid (Example 58),

[0907] 2-{4-[(4-chlorophenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 59),

[0908] 2-{4-[(4-tert-butylphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 60),

[0909] 2-{4-[(4-benzyloxyphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 61),

[0910] trans-4-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]cyclohexan-1-ol (Example 62),

[0911] trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-methoxycyclohexane (Example 63),

[0912] 2-(4-benzyloxyphenyl)-5-carboxymethyl-1-cyclopentylbenzimidazole (Example 64),

[0913] 2-[1-benzyloxycarbonyl-4-piperidyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 65),

[0914] 2-[(4-cyclohexylphenyl)carbonylamino]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 66),

[0915] 1-cyclopentyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 67),

[0916] 1-cyclopentyl-2-[4-(3,4-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 68),

[0917] 1-cyclopentyl-2-[4-(phenylcarbamoylamino)phenyl]benzimidazole-5-carboxylic acid (Example 69),

[0918] 1-cyclopentyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 70),

[0919] 1-cyclopentyl-2-(4-phenethyloxyphenyl)benzimidazole-5-carboxylic acid (Example 71),

[0920] trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-tert-butylcyclohexane (Example 72),

[0921] 2-(4-benzyloxyphenyl)-5-carboxymethoxy-1-cyclopentylbenzimidazole (Example 73),

[0922] 2-(4-benzylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 74),

[0923] 2-[4-(N-benzenesulfonyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 75),

[0924] 2-[4-(N-benzyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 76),

[0925] 1-cyclohexyl-2-(4-phenethylphenyl)benzimidazole-5-carboxylic acid (Example 77),

[0926] 2-(1-benzyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 78),

[0927] 2-(1-benzoyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 79),

[0928] 1-cyclopentyl-2-[1-(p-toluenesulfonyl)-4-piperidyl]-benzimidazole-5-carboxylic acid (Example 80),

[0929] 1-cyclohexyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 81),

[0930] 1-cyclohexyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 82),

[0931] 1-cyclohexyl-2-[4-(3,5-di-tert-butylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid (Example 83),

[0932] 2-(4-benzyloxyphenyl)-1-(4-methylcyclohexyl)benzimidazole-5-carboxylic acid (Example 84),

[0933] 1-cyclohexyl-2-{4-[2-(2-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 85),

[0934] 1-cyclohexyl-2-[4-(1-naphthyl)methoxyphenyl]benzimidazole-5-carboxylic acid (Example 86),

[0935] 1-cyclohexyl-2-[4-(dibenzylamino)phenyl]benzimidazole-5-carboxylic acid (Example 87),

[0936] 2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 88),

[0937] 2-(4-benzyloxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 89),

[0938] 1-cyclohexyl-2-[4-(dibenzylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 90),

[0939] 2-(4-benzoylmethoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 91),

[0940] 2-(4-benzyl-1-piperazinyl)-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 92),

[0941] 1-cyclohexyl-2-[4-(3,3-diphenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 93),

[0942] 2-[4-(3-chloro-6-phenylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 94),

[0943] 2-(4-benzyloxypiperidino)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 95),

[0944] 1-cyclohexyl-2-{4-[2-(phenoxy)ethoxy]pheny}benzimidazole-5-carboxylic acid (Example 96),

[0945] 1-cyclohexyl-2-[4-(3-phenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 97),

[0946] 1-cyclohexyl-2-[4-(5-phenylpentyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 98),

[0947] 2-(3-benzyloxy-5-isoxazolyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 99),

[0948] 2-(2-benzyloxy-5-pyridyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 100),

[0949] 1-cyclohexyl-2-{4-[2-(3,4,5-trimethoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 101),

[0950] 2-(4-benzyloxyphenyl)-1-(4,4-dimethylcyclohexyl)benzimidazole-5-carboxylic acid (Example 102),

[0951] 1-cyclohexyl-2-{4-[2-(1-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 103),

[0952] 2-[4-(2-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 104),

[0953] 2-[4-(3-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 105),

[0954] 1-cyclohexyl-2-[4-(2-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 106),

[0955] 1-cyclohexyl-2-[4-(3-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 107),

[0956] 1-cyclohexyl-2-[4-(2-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 108),

[0957] 1-cyclohexyl-2-[4-(3-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 109),

[0958] 1-cyclohexyl-2-[4-(2-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 110),

[0959] 1-cyclohexyl-2-[4-(3-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 111),

[0960] 1-cyclohexyl-2-{4-[2-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 112),

[0961] 1-cyclohexyl-2-{4-[3-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 113),

[0962] 1-cyclohexyl-2-[4-(2-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 114),

[0963] 1-cyclohexyl-2-[4-(3-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 115),

[0964] 1-cyclohexyl-2-{4-[2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 116),

[0965] 1-cyclohexyl-2-{4-[2-(4-trifluoromethylphenyl)benzyloxy]-phenyl}benzimidazole-5-carboxylic acid (Example 117),

[0966] 2-{4-[bis(4-chlorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 118),

[0967] 1-cyclohexyl-2-{4-[2-(4-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 119),

[0968] 1-cyclohexyl-2-{4-[2-(2-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 120),

[0969] 1-cyclohexyl-2-{4-[2-(3-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 121),

[0970] 2-(4-benzyloxyphenyl)-1-cycloheptylbenzimidazole-5-carboxylic acid (Example 122),

[0971] 1-cyclohexyl-2-[4-(2-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 123),

[0972] 1-cyclohexyl-2-[4-(3-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 124),

[0973] 1-cyclohexyl-2-[4-(2,2-diphenylethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 125),

[0974] 2-(4-benzyloxyphenyl)-1-(3-cyclohexenyl)benzimidazole-5-carboxylic acid (Example 126),

[0975] cis-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-fluorocyclohexane (Example 127),

[0976] 1-cyclohexyl-2-[4-(2-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 128),

[0977] 1-cyclohexyl-2-[4-(3-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 129),

[0978] 2-{4-[(2R)-2-benzyloxycarbonylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 130),

[0979] 1-cyclohexyl-2-{2-fluoro-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 131),

[0980] 2-[4-(4-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 132),

[0981] 2-{4-[bis(4-methylphenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 133),

[0982] 2-{4-[bis(4-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 134),

[0983] 1-cyclohexyl-6-methoxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 135),

[0984] 1-cyclohexyl-6-hydroxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 136),

[0985] 1-cyclohexyl-6-methyl-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 137),

[0986] 2-{4-[2-(2-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 138),

[0987] 2-{4-[2-(3-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 139),

[0988] 2-[4-(2-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 140),

[0989] 2-[4-(3-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 141),

[0990] 2-{4-[3-chloro-6-(4-methylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 142),

[0991] 2-{4-[3-chloro-6-(4-methoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 143),

[0992] 1-cyclohexyl-2-{2-methyl-4-[2-(4-trifluoromethylphenyl)-benzyloxy]pheny}benzimidazole-5-carboxylic acid (Example 144),

[0993] 2-{4-[2-(4-tert-butylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 145),

[0994] 2-{4-(3-chloro-6-phenylbenzyloxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 146),

[0995] 2-{4-[3-chloro-6-(3,5-dichlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 147),

[0996] 2-{4-[bis(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 148),

[0997] 2-{4-(4-benzyloxyphenoxy)-2-chlorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 149),

[0998] 2-{4-(4-benzyloxyphenoxy)-2-trifluoromethylphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 150),

[0999] 2-{4-[3-chloro-6-(2-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 151),

[1000] 2-{4-[(2R)-2-amino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 152),

[1001] 2-(4-(2-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 153),

[1002] 2-[4-(3-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 154),

[1003] 2-{4-[2-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 155),

[1004] 2-{4-[3-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 156),

[1005] 2-{4-[3-chloro-6-(3,4,5-trimethoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 157),

[1006] 2-{4-[2-(2-biphenylyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 158),

[1007] 2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 159),

[1008] 1-cyclohexyl-2-{4-[2-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride (Example 160),

[1009] 1-cyclohexyl-2-{4-[3-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride (Example 161),

[1010] 2-{4-[(2R)-2-acetylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 162),

[1011] 1-cyclohexyl-2-{4-[3-(4-methyl-3-pentenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 163),

[1012] 1-cyclohexyl-2-{4-[3-(3-methyl-3-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 164),

[1013] 2-{4-[{(2S)-1-benzyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid hydrochloride (Example 165),

[1014] 2-{4-[3-chloro-6-(4-methylthiophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 166),

[1015] 2-{4-[3-chloro-6-(4-methanesulfonylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 167),

[1016] 2-{4-[3-chloro-6-(2-thienyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 168),

[1017] 2-{4-[3-chloro-6-(3-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 169),

[1018] 2-4-[3-chloro-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 170),

[1019] 2-{4-[3-chloro-6-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 171),

[1020] 2-[4-(4-benzyloxyphenoxy)-3-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 172),

[1021] 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 173),

[1022] 2-{4-[3-chloro-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 174),

[1023] 2-{4-[2-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 175),

[1024] 2-{4-[3-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 176),

[1025] 1-cyclohexyl-2-{4-[3-(2-propynyloxy)phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 177),

[1026] 1-cyclohexyl-2-{4-[3-(3-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 178),

[1027] 2-(4-benzyloxy-2-methoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 179),

[1028] 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 180),

[1029] 2-[4-(carboxydiphenylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 181),

[1030] 2-{4-[2-(4-chlorophenyl)-5-nitrobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 182),

[1031] 2-{4-[3-acetylamino-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 183),

[1032] 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 184),

[1033] 2-{4-[{(2S)-1-benzyloxycarbonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 185),

[1034] 2-{2-chloro-4-[2-(4-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 186),

[1035] 1-cyclohexyl-2-{4-[3-(2-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 187),

[1036] 2-{4-[2-(4-chlorophenyl)-5-fluorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 188),

[1037] 2-{4-[3-carboxy-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 189),

[1038] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 190),

[1039] 1-cyclohexyl-2-{4-[2-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 191),

[1040] 1-cyclohexyl-2-{4-[2-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 192),

[1041] 2-{4-[{(2S)-1-benzenesulfonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 193),

[1042] 2-{4-[{(2S)-1-benzoyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 194),

[1043] 2-{4-[2-(4-carbamoylphenyl)-5-chlorobenzyloxy]phenyl}1-cyclohexylbenzimidazole-5-carboxylic acid (Example 195),

[1044] 1-cyclohexyl-2-{4-[3-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 196),

[1045] 1-cyclohexyl-2-{4-[3-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 197),

[1046] 1-cyclohexyl-2-{4-[3-{(1-methanesulfonyl-4-piperidyl)methoxy}-phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 198),

[1047] 1-cyclohexyl-2-{4-[{2-methyl-5-(4-chlorophenyl)-4-oxazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 199),

[1048] 2-{4-[3-(3-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 200),

[1049] 2-{4-[3-(4-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 201),

[1050] 1-cyclohexyl-2-{4-[3-(4-fluorobenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 202),

[1051] 1-cyclohexyl-2-{4-[{(2S)-1-(4-nitrophenyl)-2-pyrrolidinyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 203),

[1052] 1-cyclohexyl-2-{4-[{(2S)-1-phenyl-2-pyrrolidinyl}methoxy]-phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 204),

[1053] 2-{4-[{(2S)-1-(4-acetylaminophenyl)-2-pyrrolidinyl}methoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 205),

[1054] 2-{4-[{5-(4-chlorophenyl)-2-methyl-4-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 206),

[1055] 2-{4-[bis(3-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 207),

[1056] 1-cyclohexyl-2-{4-[2-(4-chlorophenyl)-3-nitrobenzyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 208),

[1057] 1-cyclohexyl-2-{4-[3-(4-tetrahydropyranyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 209),

[1058] 1-cyclohexyl-2-{4-[3-(4-trifluoromethylbenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 210),

[1059] 1-cyclohexyl-2-{4-[3-{(1-methyl-4-piperidyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 211),

[1060] 2-{4-[3-(4-tert-butylbenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 212),

[1061] 2-{4-[3-(2-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 213),

[1062] 1-cyclohexyl-2-{4-[3-(3-pyridyl)phenoxy]pheny}benzimidazole-5-carboxylic acid (Example 214),

[1063] 2-{4-[3-(4-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 215),

[1064] 1-cyclohexyl-2-{4-[3-(4-methoxyphenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 216),

[1065] 1-cyclohexyl-2-{4-[{4-(4-methanesulfonylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 217),

[1066] 2-{4-[{4-(4-chlorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 218),

[1067] 2-{4-[1-(4-chlorobenzyl)-3-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 219),

[1068] 1-cyclohexyl-2-{4-[3-{(2-methyl-4-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 220),

[1069] 1-cyclohexyl-2-{4-[3-{(2,4-dimethyl-5-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 221),

[1070] 1-cyclohexyl-2-{4-[3-(3,5-dichlorophenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 222),

[1071] 2-{4-[1-(4-chlorobenzyl)-4-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 223),

[1072] 2-{4-[3-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 224),

[1073] 2-{4-[4-carbamoyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 225),

[1074] 2-{4-[4-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 226),

[1075] 2-{4-[3-{(2-chloro-4-pyridyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 227),

[1076] 2-{4-[{(2S)-1-(4-dimethylcarbamoylphenyl)-2-pyrrolidinyl}-methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 228),

[1077] 2-{4-[2-(4-chlorophenyl)-5-ethoxycarbonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 229),

[1078] 1-cyclohexyl-2-[4-(3-trifluoromethylphenoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 230),

[1079] 1-cyclohexyl-2-{4-[{4-(4-dimethylcarbamoylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 231),

[1080] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 232),

[1081] 2-{4-[{4-(4-chlorophenyl)-2-methyl-5-pyrimidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 233),

[1082] 2-{4-[{2-(4-chlorophenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 234),

[1083] 2-{4-[{3-(4-chlorophenyl)-2-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 235),

[1084] 2-{4-[2-(3-chlorophenyl)-4-methylamino-1,3,5-triazin-6-yloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate (Example 236),

[1085] 2-{4-[2-(4-chlorophenyl)-4-(5-tetrazolyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 237),

[1086] 2-[4-(4-benzyloxy-6-pyrimidinyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 238),

[1087] 1-cyclohexyl-2-{4-[4-(4-pyridylmethoxy)-6-pyrimidinyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 239),

[1088] 2-{4-[4-(3-chlorophenyl)-6-pyrimidinyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 240),

[1089] methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 241),

[1090] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid hydrochloride (Example 242),

[1091] ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 243),

[1092] methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 244),

[1093] methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 245),

[1094] methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (Example 246),

[1095] methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 247),

[1096] 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 248),

[1097] 2-{4-[3-(tert-butylsulfamoyl)-6-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 249),

[1098] 2-{4-[2-(4-chlorophenyl)-5-sulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate (Example 250),

[1099] 2-(4-benzyloxycyclohexyl)-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 251),

[1100] 2-[2-(2-biphenylyloxymethyl)-5-thienyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 252),

[1101] 2-[2-(2-biphenylyloxymethyl)-5-furyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 253),

[1102] 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-hydroxymethyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 254),

[1103] 1-cyclohexyl-2-{4-[{4-(4-carboxyphenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 255),

[1104] 1-cyclohexyl-2-{2-fluoro-4-[4-fluoro-2-(3-fluorobenzoyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 256),

[1105] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-sulfonic acid (Example 257),

[1106] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexylbenzimidazole-4-carboxylic acid (Example 258),

[1107] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-5-(4-pyridylmethoxy)-phenoxy]phenyl}benzimidazole-5-carboxylic acid dihydrochloride (Example 259),

[1108] 1-cyclohexyl-2-{4-[3-carboxy-5-(4-pyridylmethoxy)phenoxy]-phenylbenzimidazole-5-carboxylic acid dihydrochloride (Example 260),

[1109] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-4-carboxylic acid (Example 261),

[1110] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 262),

[1111] 2-{4-[{2-(4-carboxyphenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 263),

[1112] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 264),

[1113] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 265),

[1114] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-trifluoromethylphenyl)benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 266),

[1115] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-methylthiophenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 267),

[1116] 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 268),

[1117] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 269),

[1118] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 270),

[1119] 2-{4-[3-dimethylcarbamoyl-6-(4-methanesulfonylphenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 271),

[1120] 2-{4-[3-dimethylcarbamoyl-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 272),

[1121] 2-{4-[3-dimethylcarbamoyl-6-(4-dimethylcarbamoylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 273),

[1122] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 274),

[1123] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 275),

[1124] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 276),

[1125] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 277),

[1126] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 278),

[1127] 2-{4-[2-(4-chlorophenyl)-5-dimethylsulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 279),

[1128] 2-{4-[2-(4-chlorophenyl)-5-methanesulfonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 280),

[1129] methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (Example 281),

[1130] 2-{4-[2-(4-chlorophenyl)-5-dimethylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 282),

[1131] 2-{4-[2-(4-chlorophenyl)-5-methanesulfonylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 283),

[1132] 2-{4-[2-(4-chlorophenyl)-5-diethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 284),

[1133] 2-{4-[2-(4-chlorophenyl)-5-isopropylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 285),

[1134] 2-{4-[2-(4-chlorophenyl)-5-piperidinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 286),

[1135] 2-{4-[2-(4-chlorophenyl)-5-(1-pyrrolidinyl)carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 287),

[1136] 2-{4-[2-(4-chlorophenyl)--5-(2-hydroxyethyl)carbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 288),

[1137] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidino)-carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 289),

[1138] 2-{4-[2-(4-chlorophenyl)-5-morpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 290),

[1139] 2-{4-[2-(4-chlorophenyl)-5-thiomorpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 291),

[1140] 2-{4-[3-(carboxymethylcarbamoyl)-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 292),

[1141] 2-{4-[2-{4-(2-carboxyethyl)phenyl}-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 293),

[1142] 2-{4-[3-chloro-6-(4-hydroxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 294),

[1143] 2-{4-[3-chloro-6-(4-methoxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 295),

[1144] 2-{4-[2-(3-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 296),

[1145] 2-{4-[2-(4-chlorophenyl)-5-methylthiobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 297),

[1146] 2-{4-[2-(4-chlorophenyl)-5-methylsulfinylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 298),

[1147] 2-{4-[2-(4-chlorophenyl)-5-cyanobenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid hydrochloride (Example 299),

[1148] 2-{4-[bis(3-pyridyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 300),

[1149] 2-{4-[bis(4-dimethylcarbamoylphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 301),

[1150] sodium 2-{4-[2-thienyl-3-thienylmethoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 302),

[1151] methyl 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 303),

[1152] sodium 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 304),

[1153] 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 305),

[1154] 2-{4-[2-(4-carboxyphenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 306),

[1155] 2-{4-[2-(4-carbamoylphenyl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 307),

[1156] 2-{4-[5-amino-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 308),

[1157] 2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 309),

[1158] 2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfonyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 310),

[1159] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzylthio]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 311),

[1160] 2-{4-[bis(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 312),

[1161] 2-[4-(phenyl-3-pyridylmethoxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 313),

[1162] methyl 2-{4-[2-(4-chlorophenyl)-5-(methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 314),

[1163] 2-{4-[5-chloro-2-(4-pyridyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 315),

[1164] 2-{4-[2-(4-chlorophenyl)-5-(benzylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 316),

[1165] 2-{4-[2-(4-chlorophenyl)-5-(cyclohexylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 317),

[1166] 2-{4-[2-(4-chlorophenyl)-5-(4-pyridylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 318),

[1167] 2-{4-[2-(4-chlorophenyl)-5-(N-benzyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 319),

[1168] methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate (Example 501),

[1169] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic acid (Example 502),

[1170] 2-(4-benzyloxyphenyl)-1-cyclopentyl-1H-indole-5-carboxylic acid (Example 503),

[1171] ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate (Example 601),

[1172] 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid (Example 602), and

[1173] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (Example 701).

[1174] (92) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of

[1175] 2-{4-[5-dimethylaminocarbonyl-2-(4-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 320),

[1176] 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperazin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 321),

[1177] 2-{4-[2-(4-chlorophenyl)-5-{N-(3-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 322),

[1178] 2-{4-[2-(4-chlorophenyl)-5-{N-(2-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 323),

[1179] 2-{4-[2-(4-chlorophenyl)-5-(cyclohexylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 324),

[1180] 2-{4-[2-(4-chlorophenyl)-5-(2-pyridin-4-ylethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 325),

[1181] 2-{4-[(4-fluorophenyl){4-(dimethylaminocarbonyl)phenyl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 326),

[1182] 2-{4-[(4-fluorophenyl)(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 327),

[1183] 2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 328),

[1184] 2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 329),

[1185] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 330),

[1186] 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 331),

[1187] 2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 332),

[1188] 2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 333),

[1189] 2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 334), and

[1190] 2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 335).

[1191] (93) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of

[1192] methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 336),

[1193] methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 337),

[1194] methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 338),

[1195] methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 339),

[1196] 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 340),

[1197] 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 341),

[1198] 2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 342),

[1199] 2-{4-[2-(4-chlorophenyl)-5-{(4-hydroxypiperidin-1-ylcarbonyl)-methoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 343),

[1200] 2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 344),

[1201] 2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 345),

[1202] 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 346),

[1203] 2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 347),

[1204] 2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 348),

[1205] 2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 349),

[1206] 2-{4-[2-(4-chlorophenyl)-4-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 350),

[1207] 2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 351),

[1208] 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 352),

[1209] 2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 353),

[1210] 2-{4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 354),

[1211] 2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 355),

[1212] 2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 356),

[1213] 2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 357),

[1214] 2-{4-[5-(2-aminothiazol-4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 358),

[1215] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 359),

[1216] 2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 360),

[1217] 2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 361),

[1218] 2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 362),

[1219] 2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 363),

[1220] 2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 364),

[1221] 2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 365),

[1222] 2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 366),

[1223] 2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 367),

[1224] 2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 368),

[1225] 2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 369),

[1226] 2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl)ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 370),

[1227] 2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 371),

[1228] 2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 372),

[1229] 2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 373),

[1230] 2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 374),

[1231] 2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadiazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 375),

[1232] 2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 376),

[1233] 2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 377),

[1234] 2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 378),

[1235] 2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 379),

[1236] 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 380),

[1237] 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 381),

[1238] 2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 382),

[1239] 2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 383),

[1240] 2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 384),

[1241] 2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 385),

[1242] 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 386),

[1243] 2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 387),

[1244] 2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 388),

[1245] 2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 389),

[1246] 2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 390),

[1247] 2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 391),

[1248] 2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 392),

[1249] 2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 393),

[1250] 2-{4-[2-(4-chlorophenyl)-5-{(ethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 394),

[1251] 2-{4-[2-(4-chlorophenyl)-5-{(isopropylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 395),

[1252] 2-{4-(2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 396),

[1253] 2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 397),

[1254] 2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 398),

[1255] 2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 399),

[1256] 2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 400),

[1257] 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 401),

[1258] 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 402),

[1259] 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 403),

[1260] 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 404),

[1261] 2-{4-[2-{4-(methylthio)phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 405),

[1262] 2-{4-[2-{4-(methylthio) phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 406),

[1263] 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 407),

[1264] 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 408),

[1265] 2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 409),

[1266] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 410),

[1267] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 411),

[1268] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 412),

[1269] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 413),

[1270] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 414),

[1271] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 415),

[1272] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 416),

[1273] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 417),

[1274] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 418),

[1275] 2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 419),

[1276] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid hydrochloride (Example 420),

[1277] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid (Example 421),

[1278] 2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 422),

[1279] 2-{4-[2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 423),

[1280] 2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 424),

[1281] 2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 425),

[1282] 2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 426),

[1283] 2-{4-[{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 427),

[1284] 2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 428),

[1285] 2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 429),

[1286] 2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 430),

[1287] 2-{4-[2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 431),

[1288] 2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 432),

[1289] 2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 433),

[1290] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole (Example 434),

[1291] 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole hydrochloride (Example 435),

[1292] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzimidazole hydrochloride (Example 436),

[1293] 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 437),

[1294] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 438),

[1295] 2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}-methyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 439),

[1296] 2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 440),

[1297] 2-{3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 441),

[1298] 2-{4-[(3-dimethylcarbamoylphenyl)(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 442),

[1299] 2-{4-[{3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 443),

[1300] 1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-&bgr;-D-glucuronic acid (Example 444),

[1301] {[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl]-1-cyclohexylbenzimidazol-5-yl]carbonyl}-&bgr;-D-glucuronic acid (Example 445),

[1302] 2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 446),

[1303] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-dimidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride (Example 702), and

[1304] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride (Example 703).

[1305] (94) A pharmaceutical composition comprising a fused ring compound of any of (42) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1306] (95) A hepatitis C virus polymerase inhibitor comprising a fused ring compound of any of (1) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1307] (96) An anti-hepatitis C virus agent comprising a fused ring compound of any of (1) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1308] (97) A therapeutic agent for hepatitis C comprising a fused ring compound of any of (42) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1309] (98) An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of (96) above and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.

[1310] (99) An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of (96) above and (b) interferon.

[1311] (100) A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of (95) above and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.

[1312] (101) A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of (95) above and (b) interferon.

[1313] (102) A benzimidazole compound of the folllowing formula [III] 58

[1314] wherein Ra36 is hydrogen atom or carboxyl-protecting group, Ra37 is cyclopentyl or cyclohexyl, and Ra38 is hydrogen atom or fluorine atom, or a salt thereof.

[1315] (103) A thiazole compound selected from the group consisting of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and 4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole, or a pharmaceutically acceptable salt thereof.

[1316] (104) A pharmaceutical composition comprising (a) the fused compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof and (b) at least one agent selected from the group consisting of an antiviral-agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.

[1317] (105) A pharmaceutical composition comprising (a) the fused compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof and (b) interferon.

[1318] (106) A method for treating hepatitis C, which comprises administering an effective amount of a fused ring compound of the formula [I] of (1) above, or a pharmaceutically acceptable salt thereof.

[1319] (107) The method of (106) above, further comprising administering an effective amount of at least one agent selected from the group consisting of an antiviral agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.

[1320] (108) The method of (106) above, further comprising administering an effective amount of interferon.

[1321] (109) A method for inhibiting hepatitis C virus polymerase, which comprises administering an effective amount of a fused ring compound of the formula [I] of (1) above, or a pharmaceutically acceptable salt thereof.

[1322] (110) The method of (109) above, further comprising administering an effective amount of at least-one agent selected from the group consisting of an antiviral agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.

[1323] (111) The method of (109) above, further comprising administering an effective amount of interferon.

[1324] (112) Use of a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof for the production of a pharmaceutical agent for treating hepatitis C.

[1325] (113) Use of a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof for the production of a hepatitis C virus polymerase inhibitor.

[1326] (114) A pharmaceutical composition for the treatment of hepatitis C, which comprises a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1327] (115) A pharmaceutical composition for inhibiting hepatitis C virus polymerase, which comprises a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1328] (116) A commercial package comprising a pharmaceutical composition of (114) above and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for treating hepatitis C.

[1329] (117) A commercial package comprising a pharmaceutical composition of (115) above and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for inhibiting hepatitis C virus polymerase.

DETAILED DESCRIPTION OF THE INVENTION

[1330] The definitions of respective substituents and moieties used in the present specification are as follows.

[1331] The halogen atom is a fluorine atom, chlorine atom, bromine atom or iodine atom, preferably fluorine atom, chlorine atom or bromine atom.

[1332] Particularly preferably, the halogen atom is fluorine atom at R5, R5′, R6, R6′, group A and group C, and fluorine atom or chlorine atom at X, Z, Z′, group B and group D.

[1333] The C1-6 alkyl is straight chain or branched chain alkyl having 1 to 6 carbon atoms, and is exemplified by methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, hexyl and the like.

[1334] Preferably, it is straight chain or branched chain alkyl having 1 to 4 carbon atoms, and is particularly preferably methyl at Ra7, Ra8, Ra9, Ra15, Ra16, Ra17, Ra29, Ra33, Ra35, Rb6 and Rb7 and methyl or tert-butyl at Rb1, Rb2, group B and group C.

[1335] The halogenated C1-6 alkyl is the above-defined C1-6 alkyl except that it is substituted by the above-defined halogen atom. Preferably, it is halogenated alkyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include fluoromethyl, difluoromethyl, trifluoromethyl, bromomethyl, chloromethyl, 1,2-dichloromethyl, 2,2-dichloromethyl, 2,2,2-trifluoroethyl and the like.

[1336] The halogenated C1-6 alkyl is particularly preferably trifluoromethyl at group B.

[1337] The C1-6 alkylene is straight chain alkylene having 1 to 6 carbon atoms, and is exemplified by methylene, ethylene, trimethylene, tetramethylene, pentamethylene or hexamethylene.

[1338] The C1-6 alkylene is preferably methylene or ethylene at Y.

[1339] The C2-6 alkenylene is straight chain alkenylene having 2 to 6 carbon atoms, and is exemplified by vinylene, propenylene, 1-butenylene, 1,3-butadienylene and the like.

[1340] The C2-6 alkenylene is preferably vinylene at Y.

[1341] The C1-6 alkoxy is alkyloxy wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkoxy wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methoxy, ethoxy, propoxy, isopropyloxy, butoxy, isobutyloxy, tert-butyloxy, pentyloxy, hexyloxy and the like.

[1342] The C1-6 alkoxy is particularly preferably methoxy at Ra2, Ra3, Ra27, Ra28, Ra33, group A and group C.

[1343] The C1-6 alkoxy C1-6 alkoxy is that wherein C1-6 alkoxy in the above definition is substituted by C1-6 alkoxy defined above and is preferably that wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Specific examples include methoxymethyl, ethoxymethyl, methoxyethoxy, methoxypropoxy, isopropyloxyethoxy and the like.

[1344] The group A is particularly preferably methoxyethoxy.

[1345] The C1-6 alkanoyl is alkylcarbonyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkanoyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include acetyl, propionyl, butyryl, isobutyryl, pivaloyl and the like.

[1346] The C1-6 alkanoyl is particularly preferably acetyl at R1, R2, R3, R4, Ra5, Ra29, Rb7 and group B.

[1347] The C1-6 alkoxycarbonyl is alkyloxycarbonyl wherein the alkoxy moiety thereof is the above-defined C1-6 alkoxy. Preferably, it is alkoxycarbonyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropyloxycarbonyl, butoxycarbonyl, isobutyloxycarbonyl, tert-butyloxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and the like.

[1348] The C1-6 alkoxycarbonyl is particularly preferably methoxycarbonyl or ethoxycarbonyl at Ra10 and group A.

[1349] The C1-6 alkylamino is alkylamino or dialkylamino wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkylamino or dialkylamino wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, methylethylamino, N-isopropyl-N-isobutylamino and the like.

[1350] The C1-6 alkylamino is particularly preferably methylamino at Ra7, and particularly preferably dimethylamino at Ra21 and group A, and particularly preferably dimethylamino, ethylamino or isopropylamino at Ra24.

[1351] The C1-6 alkanoylamino is alkylcarbonylamino wherein the alkanoyl moiety thereof is the above-defined C1-6 alkanoyl. Preferably, it is alkylcarbonylamino wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include acetylamino, propionylamino, butyrylamino, isobutyrylamino, pivaloylamino and the like.

[1352] The C1-6 alkanoylamino is particularly preferably acetylamino at X and Ra10.

[1353] The C1-6 alkylsulfonyl is alkylsulfonyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkylsulfonyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl and the like.

[1354] The C1-6 alkylsulfonyl is particularly preferably methylsulfonyl at X and Ra5.

[1355] The C6-14 aryl is aromatic hydrocarbon having 6 to 14 carbon atoms. Examples thereof include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl and the like.

[1356] The C6-14 aryl is preferably phenyl or naphthyl, particularly preferably phenyl at the ring A, ring A′, ring B and ring B′.

[1357] The C3-8 cycloalkyl is saturated cycloalkyl having 3 to 8, preferably 5 to 7, carbon atoms. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

[1358] The C3-8 cycloalkyl is particularly preferably cyclohexyl at the ring A, ring A′, ring B and ring B′.

[1359] The C3-8 cycloalkenyl is cycloalkenyl having 3 to 8, preferably 5 to 7, carbon atoms and has at least 1, preferably 1 or 2, double bond(s). Examples thereof include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, cycloheptenyl and cyclooctenyl and the like, but do not include aryl (e.g., phenyl) or completely saturated cycloalkyl.

[1360] The C3-8 cycloalkenyl is preferably cyclohexenyl at the ring A and ring A′.

[1361] The heterocyclic group has, as an atom constituting the ring, 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, besides a carbon atom, and includes saturated ring and unsaturated ring, monocyclic ring and fused ring having the number of ring atom constituting the ring of 3 to 14.

[1362] The heterocyclic group as a monocyclic ring includes, for example, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl and the like.

[1363] The heterocyclic group includes the groups of the following formulas. 59

[1364] wherein E1 is an oxygen atom, a sulfur atom or N(—Ra35), E2 is an oxygen atom, CH2 or N(—Ra35), E3 is an oxygen atom or a sulfur atom, wherein Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and h′ are the same or different and each is an integer of 1 to 3.

[1365] Specific examples of the heterocyclic group include 60

[1366] and the like.

[1367] Examples of the heterocyclic group as a fused ring include quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydro-2-oxobenzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl and the like.

[1368] Preferably, it is a heterocyclic group which is a 5-membered or a 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl 61

[1369] and the like.

[1370] At R1, R2, R3, R4, Z and group D, tetrazolyl and 5-oxo-&Dgr;2-1,2,4-oxadiazolin-3-yl are particularly preferable.

[1371] The heterocyclic group is preferably pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl which is an aromatic group, and particularly preferably pyridyl at the ring A and ring A′.

[1372] The heterocyclic group is particularly preferably pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or thiadiazolyl, which is an aromatic group, at the ring B and ring B′. More preferably it is pyridyl or thiazolyl, most preferably thiazolyl.

[1373] The C6-14 aryl C1-6 alkyl is arylalkyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl and the aryl moiety is the above-defined C6-14 aryl. Preferably, it is arylalkyl wherein the alkyl moiety thereof is straight chain alkyl having 1 to 4 carbon atoms and the aryl moiety is phenyl. Examples thereof include benzyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl and the like.

[1374] The C6-14 aryl C1-6 alkyl is particularly preferably benzyl at Ra8 and Rb6.

[1375] The glucuronic acid residue is glucuronic acid less any hydroxyl group, preferably &bgr;-D-glucuronic acid substituted at 1-position.

[1376] The C6-14 aryl C1-6 alkyloxycarbonyl is arylalkyloxycarbonyl wherein the C6-14 aryl C1-6 alkyl moiety thereof is the above-defined C6-14 aryl C1-6 alkyl. Preferably, it is arylalkyloxycarbonyl wherein the alkyl moiety thereof is straight chain alkyl having 1 to 4 carbon atoms and the aryl moiety is phenyl. Examples thereof include benzyloxycarbonyl, phenethyloxycarbonyl, 3-phenylpropyloxycarbonyl, 2-phenylpropyloxycarbonyl, 4-phenylbutyloxycarbonyl and the like.

[1377] The C6-14 aryl C1-6 alkyloxycarbonyl is particularly preferably benzyloxycarbonyl at Rb7.

[1378] The optionally substituted C1-6 alkyl is the above-defined C1-6 alkyl, preferably that wherein straight chain or branched chain alkyl having 1 to 4 carbon atoms is optionally substituted with 1 to 3 substituent(s), and includes unsubstituted alkyl. The substituent(s) is(are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino, the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxy C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples of optionally substituted C1-6 alkyl include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, neopentyl, 1-ethylpropyl, hexyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 1-hydroxy-1-methylethyl, 1-hydroxypropan-2-yl, 1,3-dihydroxypropan-2-yl, 1-hydroxy-2-methylpropan-2-yl, carboxylmethyl, 2-carboxylethyl, methoxymethyl, methoxyethyl, methoxyethoxyethyl, ethoxycarbonylmethyl, 2-ethoxycarbonylethyl, 2-dimethylaminoethyl and the like.

[1379] Preferably, the optionally substituted C1-6 alkyl is methyl, 1-hydroxy-1-methylethyl, carboxylmethyl or 2-dimethylaminoethyl at R1, R2, R3 and R4, methyl or trifluoromethyl at R5, R5′, R6 and R6′, methyl at R7, R8, Ra25, Ra31 and Rb5, methyl, ethyl or isopropyl at Ra24, methyl or isopropyl at Ra18, methyl or ethyl at Ra1 and Ra19, methyl, carboxylmethyl or 2-dimethylaminoethyl at Ra2 and Ra3, methyl or carboxylmethyl at Ra6, methyl, ethyl, isopropyl, butyl or trifluoromethyl at X, methyl, ethyl, isopropyl, butyl, isobutyl, tert-butyl, isopentyl, neopentyl, 1-ethylpropyl or carboxylmethyl at Ra10, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, trifluoromethyl, 2-hydroxyethyl or carboxylmethyl at Ra11, methyl or 4-hydroxybutyl at Ra12, methyl, ethyl, isopropyl, butyl, 2-hydroxyethyl, 4-hydroxybutyl, ethoxycarbonylmethyl, 2-(ethoxycarbonyl)ethyl or 2-dimethylaminoethyl at Ra13, methyl, propyl, butyl, isopentyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, methoxyethyl, methoxyethoxyethyl or carboxymethyl at Ra20, methyl or ethyl at Ra22 and Ra32, methyl isopropyl or tert-butyl at Ra26, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, 2-hydroxyethyl 1-hydroxypropan-2-yl, 1-hydroxy-2-methylpropan-2-yl or carboxylmethyl at Ra27 and Ra28, and methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 2-carboxylethyl, methoxymethyl or ethoxycarbonylmethyl at Z, Z′ and group D.

[1380] It is particularly preferably, trifluoromethyl at R5, R5′, R6 and R6′, methyl or tert-butyl at Ra26, methyl, tert-butyl, trifluoromethyl or hydroxymethyl at Z, Z′ and group D, and methyl at other substituents.

[1381] The optionally substituted C2-6 alkenyl is that wherein straight chain or branched chain alkenyl having 2 to 6 carbon atoms is optionally substituted by 1 to 3 substituent(s), and includes unsubstituted alkenyl. The substituent(s) is(are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxy C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples of optionally substituted C2-6 alkenyl include vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 1,3-butadienyl, 2-isopentenyl, 3-isohexenyl, 4-methyl-3-pentenyl, 2-carboxylethenyl and the like.

[1382] The optionally substituted C2-6 alkenyl is preferably 2-carboxylethenyl at X, and preferably 2-isopentenyl, 3-isohexenyl or 4-methyl-3-pentenyl at Ra20.

[1383] The optionally substituted C2-6 alkynyl is that wherein straight chain or branched chain alkynyl having 2 to 6 carbon atoms is optionally substituted by 1 to 3 substituent(s), and includes unsubstituted alkynyl. The substituent(s) is (are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino, the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples thereof include ethynyl, 1-propynyl, 2-propynyl, 3-butynyl and the like.

[1384] The optionally substituted C2-6 alkynyl is preferably 2-propynyl at Ra20.

[1385] The C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined C6-14 aryl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the above-defined halogen atom, cyano, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 (wherein Rb1 and Rb2 are each independently hydrogen atom or the above-defined C1-6 alkyl and r is 0 or an integer of 1 to 6).

[1386] Examples thereof include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, pentafluorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-nitrophenyl, 4-cyanophenyl, 4-acetylphenyl, 4-carboxylphenyl, 4-carbamoylphenyl, 4-aminophenyl, 4-dimethylaminophenyl, 4-acetylaminophenyl, 4-(methylsulfonylamino)phenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-methylthiophenyl, 4-methylsulfonylphenyl, 4-aminosulfonylphenyl, 3-nitro-4-methoxyphenyl and 4-nitro-3-methoxyphenyl.

[1387] The aryl moiety is preferably phenyl, the group B here is preferably the above-defined halogen atom, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl or —(CH2)r—ORb1. Examples of group B include fluorine atom, chlorine atom, nitro, methyl, tert-butyl, trifluoromethyl and methoxy. Particularly preferably, it is fluorine atom or chlorine atom.

[1388] With regard to “C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group B”, it is preferably phenyl, 4-tert-butylphenyl, 4-fluorophenyl, 3-chlorophenyl, chlorophenyl, 4-methoxyphenyl or 4-trifluoromethylphenyl at Ra12, Ra27 Ra28, phenyl at Ra14, Ra22, Ra23, Ra26 and Rb5, phenyl or 3-fluorophenyl at Ra18, phenyl or 2,4-dichlorophenyl at Ra20, phenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 3,5-dichlorophenyl, nitro-4-methoxyphenyl or 4-nitro-3-methoxyphenyl at Ra24, and phenyl or 4-methylphenyl at Ra25.

[1389] It is particularly preferably phenyl at other substituents.

[1390] The C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C6-14 aryl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the above-mentioned group D (substituents shown under (a) to (q)).

[1391] Examples of group D here include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, propyloxy, isopropyloxy, isopentyloxy, 2-isopentenyloxy, 3-isohexenyloxy, 4-methyl-3-pentenyloxy, 2-propynyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl and tetrazolyl.

[1392] Examples of C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 4-bromophenyl, 4-nitrophenyl, pentafluorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, 4-acetylaminophenyl, 4-cyanophenyl, 4-acetylphenyl, 4-aminophenyl, 4-dimethylaminophenyl, 4-(methylsulfonylamino)phenyl, 4-methylsulfinylphenyl, 4-aminosulfonylphenyl and 3-nitro-4-methoxyphenyl, 4-nitro-3-methoxyphenyl and 4-tetrazol-5-ylphenyl.

[1393] At Z and Z′, the aryl moiety is preferably phenyl, and group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26,

[1394] Examples of C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D preferably include phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, 4-acetylaminophenyl, 4-methylsulfinylphenyl, 4-aminosulfonylphenyl, 4-cyanophenyl and 4-tetrazolylphenyl.

[1395] Particularly preferably, it is the above-defined halogen atom, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20 or —(CH2)t—S(O)q—Ra25, which is specifically fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino. More preferably, it is fluorine atom, chlorine atom, methyl, tert-butyl, carboxyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino, most preferably fluorine atom or chlorine atom.

[1396] The heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined heterocyclic group is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocyclic group. The substituent(s) is(are) selected from the above-defined halogen atom, cyano, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or the above-defined C1-6 alkyl and r is 0 or an integer of 1 to 6.

[1397] Examples thereof include 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 4-chloropyridin-3-yl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, 2-thienyl, 3-thienyl, furyl, oxazolyl, 2-methyloxazol-4-yl, isoxazolyl, thiazolyl, 2-methylthiazol-4-yl, 2,5-dimethylthiazol-4-yl, 2,4-dimethylthiazol-5-yl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, 3-hydroxypyrrolidinyl, imidazolidinyl, azetidinyl, piperidyl, 3-hydroxypiperidino, 4-hydroxypiperidino, 3,4-dihydroxypiperidino, 4-methoxypiperidino, 4-carboxypiperidino, 4-(hydroxymethyl)piperidino, 2-oxopiperidino, 4-oxopiperidino, 2,2,6,6-tetramethylpiperidino, 2,2,6,6-tetramethyl-4-hydroxypiperidino, N-methylpiperidin-4-yl, N-(tert-butoxycarbonyl)piperidin-4-yl, N-acetylpiperidin-4-yl, N-methylsulfonylpiperidin-4-yl, piperazinyl, 4-methylpiperazinyl, 4-methylsulfonylpiperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl, tetrahydropyranyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolyl, benzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl, 62 63

[1398] and the like.

[1399] The heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or a 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the group B here is preferably the above-defined halogen atom, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2 or —(CH2)r—ORb1.

[1400] Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group B preferably include piperidino, 4-methylpiperidino, 2,6-dimethylpiperidino, 4-hydroxypiperidino, 1-piperazinyl, 1-(methylsulfonyl)piperidin-4-yl, 1-pyrrolidinyl, morpholino, 4-thiomorpholinyl, tetrahydropyranyl, pyridyl, thiazolyl, 64

[1401] Particularly preferably, it is piperidino, 4-methylpiperidino, 2,6-dimethylpiperidino, 4-hydroxypiperidino, 1-piperazinyl, 1-pyrrolidinyl, morpholino or 4-thiomorpholinyl at Ra18, tetrahydropyranyl or 4-hydroxypiperidino at Ra20, piperidino, 4-hydroxypiperidino or 3,4-dihydroxypiperidino at Ra21, pyridyl or morpholino at Ra24, pyridyl or 4-hydroxypiperidino at Ra25, pyridyl or thiazolyl at Ra25 and at Ra26 and Ra28, it is 1-(methylsulfonyl)piperidin-4-yl, 3-hydroxypyrrolidinyl, 3-hydroxypiperidino, 4-hydroxypiperidino, 3,4-dihydroxypiperidino, 4-methoxypiperidino, 4-carboxypiperidino, 4-(hydroxymethyl)piperidino, 2-oxopiperidino, 4-oxopiperidino, 2,2,6,6-tetramethylpiperidino, 2,2,6,6-tetramethyl-4-hydroxypiperidino, 4-methylsulfonylpiperazinyl, 1-oxothiomorpholin-4-yl or 1,1-dioxothiomorpholin-4-yl, and 2-oxazolin-2-yl at Ra22 and Ra23.

[1402] The heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined heterocyclic group is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocyclic group. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).

[1403] Examples of the group D here include the substituent(s) exemplified for C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.

[1404] Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 4-chloropyridin-3-yl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, 2-thienyl, 3-thienyl, furyl, oxazolyl, 2-methyloxazol-4-yl, isoxazolyl, thiazolyl, 2-methylthiazol-4-yl, 2,5-dimethylthiazol-4-yl, 2,4-dimethylthiazol-5-yl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, imidazolidinyl, piperidyl, N-methylpiperidin-4-yl, N-(tert-butoxycarbonyl)piperidin-4-yl, N-acetylpiperidin-4-yl, N-methylsulfonylpiperidin-4-yl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolinyl, benzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl 65

[1405] and the like.

[1406] In addition, the heterocyclic group may be substituted at the 3-, 4-, 5- or 6-position of 2-pyridyl, at the 2-, 4-, 5- or 6-position of 3-pyridyl, at the 2-, 3-, 5- or 6-position of 4-pyridinyl, at the 3-, 4- or 5-position of 2-thienyl, or at the 2-, 4- or 5-position of 3-thienyl, by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl, amino or acetylamino.

[1407] At Z and Z′, the heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, 2-oxopyrrolidinyl, 2-oxopiperidyl, pyrazolyl, imidazolyl, 2-imidazolinyl, 2-oxoimidazolidinyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, 2-oxazolinyl, thiazolyl, isothiazolyl, 1,1-dioxoisothiazolidinyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, &Dgr;2-1,2,4-oxadiazolyl, 5-oxo-&Dgr;2-1,2,4-oxadiazolyl, 5-oxo-&Dgr;2-1,2,4-thiadiazolinyl and 2-oxo-3H-1,2,3,5-oxathiadiazolinyl. The group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26.

[1408] Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D preferably include piperidino, 4-hydroxypiperidino, 2-oxopiperidin-1-yl, 1-piperazinyl, 1-pyrrolidinyl, 2-oxopyrrolidin-1-yl, morpholino, 4-thiomorpholinyl, 4-tetrahydropyranyl, 3-pyridyl, 2-pyrimidinyl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 5-tetrazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-&Dgr;2-oxazolin-2-yl, 2-thienyl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-&Dgr;2-1,2,4-oxadiazolin-3-yl, 5-oxo-&Dgr;2-1,2,4-thiadiazolin-3-yl and 2-oxo-3H-1,2,3,5-oxathiazolin-4-yl.

[1409] Particularly preferably, it is pyridyl, pyrimidinyl, tetrazolyl, thienyl, piperidyl, 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-&Dgr;2-oxazolin-2-yl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-&Dgr;2-1,2,4-oxadiazolin-3-yl, 5-oxo-&Dgr;2-1,2,4-thiadiazolin-3-yl or 2-oxo-3H-1,2,3,5-oxathiadiazolin-4-yl, more preferably 2-oxopyrrolidin-1-yl.

[1410] The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group C is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by the 1 to 5 substituent(s) selected from hydroxyl group, the above-defined halogen atom, the above-defined C1-6 alkyl and the above-defined C1-6 alkoxy, which may be unsubstituted. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.

[1411] The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, particularly preferably cyclohexyl.

[1412] At the ring Cy and ring Cy′, the C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group C is preferably cyclopentyl, cyclohexyl, 4-fluorocyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl or 4-methoxycyclohexyl, more preferably cyclopentyl or cyclohexyl, particularly preferably cyclohexyl.

[1413] The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkyl. The substituents are selected from the above group B.

[1414] Specific examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.

[1415] Also exemplified are those wherein cyclopentyl or cyclohexyl is substituted by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.

[1416] At cycloalkyl moiety, it is preferably cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. As the C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, it is particularly preferably cyclopropyl, cyclobutyl, cyclohexyl or 4-hydroxycyclohexyl at Ra27 and Ra28.

[1417] The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkyl. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).

[1418] The group D here includes the substituents recited with regard to C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.

[1419] Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.

[1420] The group D may be, for example, cyclopentyl or cyclohexyl substituted by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.

[1421] The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, and at Z and Z′, it is particularly preferably cyclohexyl.

[1422] The optionally substituted C3-8 cycloalkenyl is that wherein the above-defined C3-8 cycloalkenyl is optionally substituted by substituent(s) selected from hydroxyl group, the above-defined halogen atom, the above-defined C1-6 alkyl and the above-defined C1-6 alkoxy, which may be unsubstituted. Examples thereof include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, 4-fluoro-2-cyclohexenyl, 4-methyl-2-cyclohexenyl, 4-methyl-3-cyclohexenyl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, cycloheptenyl and cyclooctenyl and the like, but do not include aryl (e.g., phenyl) or completely saturated cycloalkyl.

[1423] The optionally substituted C3-8 cycloalkenyl is particularly preferably cyclohexenyl at the ring Cy.

[1424] The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined C6-14 aryl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted arylalkyl. The substituent(s) is(are) selected from the above-mentioned group B.

[1425] Examples thereof include benzyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl, 3,5-dichlorobenzyl, pentafluorobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-nitrobenzyl, 4-cyanobenzyl, 4-acetylbenzyl, 4-carboxylbenzyl, 4-carbamoylbenzyl, 4-aminobenzyl, 4-dimethylaminobenzyl, 4-acetylaminobenzyl, 4-(methylsulfonylamino)benzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-methylthiobenzyl, 4-methylsulfonylbenzyl, 4-aminosulfonylbenzyl, 3-nitro-4-methoxybenzyl and 4-nitro-3-methoxybenzyl.

[1426] The C6-14 aryl C1-6 alkyl moiety is preferably benzyl or phenethyl, particularly preferably benzyl. The group B is preferably the above-defined halogen atom, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl or —(CH2)r—ORb1. Examples thereof include fluorine atom, chlorine atom, nitro, methyl, tert-butyl, trifluoromethyl, methoxy or trifluoromethyloxy, particularly preferably fluorine atom or chlorine atom.

[1427] The specific C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B at Ra12 and Ra13 is preferably benzyl, phenethyl, 3-chlorobenzyl, 4-chlorobenzyl, 4-tert-butylbenzyl or 3-trifluoromethylbenzyl, it is preferably benzyl at Ra1, Ra19, Ra27, Ra28, Ra31 and Rb5, it is preferably benzyl, phenethyl, 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 4-tert-butylbenzyl or 4-trifluoromethylbenzyl at Ra20, and 4-chlorobenzyl, 3,5-dichlorobenzyl or 4-trifluoromethylbenzyl at Ra22 and Ra23.

[1428] It is particularly preferably benzyl at other substituents.

[1429] The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C6-14 aryl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).

[1430] Examples of group D include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, isopropyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl and dimethylaminosulfonyl.

[1431] Examples of C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include benzyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl, 3,5-dichlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl, pentafluorobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-(hydroxymethyl)benzyl, 4-(methoxymethyl)benzyl, 4-(2-carboxylethyl)benzyl, 3-carboxylbenzyl, 4-carboxylbenzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-carbamoylbenzyl, 4-methylthiobenzyl, 4-(dimethylaminocarbonyl)benzyl, 4-methylsulfonylbenzyl, 4-(acetylamino) benzyl, 4-cyanobenzyl, 4-acetylbenzyl, 4-aminobenzyl, 4-dimethylaminobenzyl, 4-(methylsulfonylamino)benzyl, 4-methylsulfinylbenzyl, 4-aminosulfonylbenzyl, (3-nitro-4-methoxyphenyl)methyl and (4-nitro-3-methoxyphenyl)methyl.

[1432] At Z and Z′, the C6-14 aryl C1-6 alkyl moiety is preferably benzyl or phenethyl, and the group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26.

[1433] The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is preferably benzyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 3,5-dichlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-(hydroxymethyl)benzyl, 4-(methoxymethyl)benzyl, 4-(2-carboxylethyl)benzyl, 3-carboxylbenzyl, 4-carboxylbenzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-carbamoylbenzyl, 4-methylthiobenzyl, 4-(dimethylaminocarbonyl)benzyl, 4-methylsulfonylbenzyl, 4-acetylaminobenzyl, 4-methylsulfinylbenzyl or 4-aminosulfonylbenzyl.

[1434] It is particularly preferably the above-defined halogen atom, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20 or —(CH2)t—S(O)q—Ra25. Examples thereof include fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl and acetylamino. It is more preferably fluorine atom, chlorine atom, methyl, tert-butyl, carboxyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl or methylsulfonyl, most preferably fluorine atom or chlorine atom.

[1435] The heterocycle C1-6 alkyl-optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined heterocycle C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocycle C1-6 alkyl. The substituent(s) is(are) selected from the above-mentioned group B.

[1436] Examples thereof include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, pyrrolylmethyl, imidazolylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 2-oxazolylmethyl, 5-isothiazolylmethyl, 2-methyloxazol-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 5-thiazolylmethyl, 2-methylthiazol-4-ylmethyl, 2-methylthiazol-5-ylmethyl, 2,5-dimethylthiazol-4-ylmethyl, 4-methylthiazol-2-ylmethyl, 2,4-dimethylthiazol-5-ylmethyl, 2-isothiazolylmethyl, 2-pyrrolinylmethyl, pyrrolidinylmethyl, piperidylmethyl, 4-piperidylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 3-hydroxypyrrolidinylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-acetylpiperidin-4-ylmethyl, 1-methylsulfonylpiperidin-4-ylmethyl, piperazinylmethyl, morpholinomethyl, thiomorpholinylmethyl, 1-tetrahydropyranylmethyl, 2-quinolylmethyl, 1-isoquinolylmethyl and the like.

[1437] The heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the alkyl moiety thereof is preferably straight chain alkyl having 1 to 4 carbon atoms. The group B here is preferably the above-defined halogen atom, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2 or —(CH2)r—ORb1.

[1438] Examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B preferably include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)-piperidin-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl and 4-methylthiazol-2-ylmethyl. Particularly preferably, it is 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)piperidin-4-ylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl or 4-methylthiazol-2-ylmethyl at Ra20, 2-pyridylmethyl at Ra22 and Ra23, and 4-pyridylmethyl or 4-methylthiazol-2-ylmethyl at Ra27 and Ra28.

[1439] The heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined heterocycle C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocycle C1-6 alkyl. The substituent(s) is(are) selected from the above-mentioned group D (substituents shown under (a) to (q)).

[1440] Examples of group D here include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, isopropyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl and dimethylaminosulfonyl.

[1441] Examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, pyrrolylmethyl, imidazolylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 2-oxazolylmethyl, 5-isothiazolylmethyl, 2-methyloxazol-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 5-thiazolylmethyl, 2-methylthiazol-4-ylmethyl, 2-methylthiazol-5-ylmethyl, 2,5-dimethylthiazol-4-ylmethyl, 4-methylthiazol-2-ylmethyl, 2,4-dimethylthiazol-5-ylmethyl, 2-isothiazolylmethyl, 2-pyrrolinylmethyl, pyrrolidinylmethyl, piperidylmethyl, 4-piperidylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 2-(4-hydroxypiperidino)ethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-acetylpiperidin-4-ylmethyl, 1-methylsulfonylpiperidin-4-ylmethyl, piperazinylmethyl, morpholinomethyl, thiomorpholinylmethyl, 1-tetrahydropyranylmethyl, 2-quinolylmethyl, 1-isoquinolylmethyl, and the like.

[1442] Preferable heterocyclic moiety at Z and Z′ is heterocylic group which is 5-membered or 6-membered monocyclic group. Examples of the heterocyclic moiety include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the alkyl moiety is preferably straight chain alkyl having 1 to 4 carbon atoms, particularly methyl (i.e., methylene).

[1443] Preferable group D is the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26.

[1444] Preferable examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)piperidin-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl and 4-methylthiazol-2-ylmethyl.

[1445] Particularly preferred is 4-hydroxypiperidinomethyl.

[1446] The C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B is that wherein the above-defined C3-8 cycloalkyl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkylalkyl. The substituents are selected from the above group B.

[1447] Specific examples thereof include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-(cyclopentyl)ethyl, 2-(cyclohexyl)ethyl, cycloheptylmethyl, 4-fluorocyclohexylmethyl, 2-methylcyclopentylmethyl, 3-methylcyclohexylmethyl, 4-methylcyclohexylmethyl, 4,4-dimethylcyclohexylmethyl, 3,5-dimethylcyclohexylmethyl, 4-tert-butylcyclohexylmethyl, 4-hydroxycyclohexylmethyl, 4-methoxycyclohexylmethyl and 2,3,4,5,6-pentafluorocyclohexylmethyl.

[1448] Also exemplified are those wherein cyclopentylmethyl or cyclohexylmethyl is substituted by fluorine atom, chlorine atom, bromine atom, nito, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.

[1449] At cycloalkyl moiety, it is preferably cyclopentylmethyl or cyclohexylmethyl, and at Ra20, Ra27 and Ra28, it is particularly preferably cyclohexylmethyl.

[1450] The carboxyl-protecting group only needs to be suitable for reaction conditions, and is capable of protecting and deprotecting and may be, for example, methyl; substituted methyl group such as methoxymethyl, methylthiomethyl, 2-tetrahydropyranyl, methoxyethoxymethyl, benzyloxymethyl, phenacyl, diacylmethyl, phthalimidomethyl etc.; ethyl; substituted ethyl group such as 2,2,2-trichloroethyl, 2-chloroethyl, 2-(trimethylsilyl)ethyl, 2-methylthioethyl, 2-(p-toluenesulfonyl)ethyl, t-butyl etc.; benzyl; substituted benzyl group such as diphenylmethyl, triphenylmethyl, p-nitrobenzyl, 4-picolyl, p-methoxybenzyl, 2-(9,10-dioxo)anthrylmethyl etc.; silyl group such as trimethylsilyl, t-butyldimethylsilyl, phenyldimethylsilyl etc.; and the like.

[1451] Preferred are industrially effective protecting groups and specifically preferred as Ra36 are methyl and ethyl.

[1452] In formula [I], X is preferably 66

[1453] wherein each symbol is as defined above.

[1454] G1, G2, G3 and G4 are each preferably (C—R1), (C—R2), (C—R3) and (C—R4), G5 is preferably a nitrogen atom, and G6, G8 and G9 are preferably a carbon atom. G7 is preferably C(—R7) or unsubstituted nitrogen atom, wherein R7 is preferably hydrogen atom.

[1455] A preferable combination is G2 of (C—R2) and G6 of a carbon atom, particularly preferably G2 of (C—R2), G6 of a carbon atom and G5 of a nitrogen atom, most preferably G2 of (C—R2), G6 of a carbon atom, G5 of a nitrogen atom and G7 of unsubstituted nitrogen atom.

[1456] In formulas [I] and [II], 1 to 4 of G1 to G9 in the moiety 67

[1457] is(are) preferably a nitrogen atom, specifically preferably 68 69

[1458] particularly preferably 70

[1459] more preferably 71

[1460] most preferably 72

[1461] It is also a preferable embodiment wherein the 73

[1462] moiety is aromatic ring.

[1463] R1 and R4 are preferably hydrogen atom. R2 is preferably carboxyl, —COORa1, —CONRa2Ra3, —SO2Ra7 (each symbol is as defined above) or heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, particularly preferably carboxyl, —COORa1 or —SO2Ra7, more preferably carboxyl or —COORa1, most preferably carboxyl. R3 is preferably hydrogen atom or —ORa6 (Ra6 is as defined above), particularly preferably hydrogen atom.

[1464] Ra1 is preferably optionally substituted C1-6 alkyl.

[1465] When R2 is carboxyl or —COORa1, at least one of R1, R3 and R4 is preferably hydroxyl group, halogen atom (particularly fluorine atom, chlorine atom) or —ORa6 (wherein Ra6 is preferably hydrogen atom or methyl).

[1466] The ring Cy and ring Cy′ are preferably cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino, particularly preferably cyclopentyl, cyclohexyl or cycloheptyl, more preferably cyclohexyl.

[1467] The ring A and ring A′ are preferably phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl or thienyl, particularly preferably phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, more preferably phenyl or pyridyl, and most preferably phenyl.

[1468] The ring B and ring B′ are preferably C1-6 aryl or heterocyclic group, specifically preferably, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or thiadiazolyl, particularly preferably phenyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl or thiazolyl, more preferably, phenyl, pyridyl or thiazolyl, and most preferably phenyl or thiazolyl.

[1469] With regard to R5 and R6, one of them is preferably hydrogen atom and the other is halogen atom, particularly fluorine atom. Alternatively, the both arepreferably hydrogen atoms. When ring A is phenyl, R5 and R6 preferably are present at an ortho position from G6. The same applies to R5′ and R6′.

[1470] Y is preferably —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (each symbol is as defined above), more preferably, —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n—, most preferably —O—(CH2)m—CRa15Ra16—(CH2)n—.

[1471] The l, m and n are preferably 0 or an integer of 1 to 4, particularly preferably 0, 1 or 2, at Y. In —(CH2)m—O—(CH2)n—, m=n=0 or m=0 and n=1 is more preferable, most preferably m=n=0. In —O—(CH2)m—CRa15Ra16—(CH2)n—, m=n=0, m=0 and n=1, m=1 and n=0 or m=1 and n=1 is more preferable, most preferably m=n=0.

[1472] When Y is —O—(CH2)m—CRa15Ra16—(CH2)n—, Ra16 is preferably hydrogen atom, Ra15 is preferably 74

[1473] wherein the 75

[1474] moiety is preferably symmetric. The preferable mode of n, ring B, Z and w and the preferable mode of n′, ring B′, Z′ and w′ are the same.

[1475] When ring A is phenyl, X or Y is preferably present at the para-position relative to G6. When ring B and ring B′ are phenyl, Z is preferably present at the ortho or meta-position relative to Y. It is preferable that the 3-position on phenyl have one substituent or the 2-position and the 5-position on phenyl each have one substituent.

[1476] When ring B is thiazolyl, Y is preferably)substituted at the 5-position, and Z is preferably substituted at the 2-position, the 4-position or the 2-position and the 4-position. Similarly, when ring B′ is thiazolyl, (CH2)n′ is also preferably substituted at the 5-position, and Z′ is preferably substituted at the 2-position, the 4-position or the 2-position and the 4-position.

[1477] Z and Z′ are preferably group D, “C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D” or “heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D”, particularly preferably group D or “C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D”.

[1478] More preferably, they are the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26, or C6-14 aryl or heterocyclic group optionally substituted by these.

[1479] With regard to Z and Z′, the preferable mode of group D that directly substitutes each ring B and ring B′ and the preferable mode of group D that substitutes C6-14 aryl, C3-8 cycloalkyl, C6-14 aryl C1-6 alkyl or heterocyclic group are the same, wherein they may be the same with or different from each other.

[1480] Specific examples of the substituent preferably include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, carbamoylmethoxymethyl, (dimethylaminocarbonyl)methoxymethyl, acetyl, isovaleryl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, hydroxyaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, isobutylaminocarbonyl, tert-butylaminocarbonyl, (4-hydroxybutyl)aminocarbonyl, (1-hydroxypropan-2-yl)aminocarbonyl, (2,3-dihydroxypropyl)-aminocarbonyl, (1,3-dihydroxypropan-2-yl)aminocarbonyl, methoxyaminocarbonyl, {2-[2-(methoxy)ethoxy]ethyl}aminocarbonyl, N-ethyl-N-methylaminocarbonyl, N-methyl-N-propylaminocarbonyl, N-isopropyl-N-methylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (2-hydroxy-2-methylpropan-2-yl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isopentyloxy, 2-isopentenyloxy, 3-isohexenyloxy, 4-methyl-3-pentenyloxy, 2-propynyloxy, trifluoromethyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)-methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, N-acetyl-N-methylamino, ureido, isopropylcarbonylamino, isobutylcarbonylamino, tert-butylcarbonylamino, (ethylamino)carbonylamino, (isopropylamino)-carbonylamino, (dimethylamino)carbonylamino, (4-hydroxypiperidino)carbonylamino, [(4-hydroxypiperidino)methyl]-carbonylamino, [(3-hydroxypyrrolidinyl)methyl]carbonylamino, methylsulfonylamino, isopropylsulfonylamino, N-(isopropylsulfonyl)-N-methylamino, methylthio, methylsulfonyl, isopropylsulfonyl, isobutylsulfonyl, methylsulfinyl, isopropylsulfinyl, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl, isopropylaminosulfonyl, tert-butylamino-sulfonyl, hydroxyamidino, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-2-fluorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-cyanophenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(2-hydroxyethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 4-(methoxycarbonylmethyl)phenyl, 4-(ethoxycarbonylmethyl)phenyl, 4-acetylphenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-(methoxycarbonyl)phenyl, 4-(ethoxycarbonyl)phenyl, 4-carbamoylphenyl, 4-(methylaminocarbonyl)phenyl, 4-(isopropylaminocarbonyl)phenyl, 4-(dimethylaminocarbonyl)phenyl, 4-(diethylaminocarbonyl)phenyl, 4-[(2-hydroxyethyl)-aminocarbonyl]phenyl, 4-[(carboxylmethyl)aminocarbonyl]phenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-ethoxyphenyl, 4-propyloxyphenyl, 4-isopropyloxyphenyl, 4-butyloxyphenyl, 4-isopentyloxyphenyl, 4-(2-isopentenyloxy)phenyl, 4-(3-isohexenyloxy)phenyl, 4-(4-methyl-3-pentenyloxy)phenyl, 4-(2-propynyloxy)phenyl, 4-(trifluoromethyloxy)phenyl, 4-(hydroxymethyloxy)phenyl, 4-(carboxylmethyloxy)phenyl, 4-[(dimethylaminocarbonyl)methyloxy]phenyl, 4-aminophenyl, 4-(methylamino)phenyl, 4-(dimethylaminophenyl), 4-(diethylamino)-phenyl, 4-(acetylamino)phenyl, 4-(methylsulfonylamino)phenyl, 4-(methylthio)phenyl, 4-(methylsulfonyl)phenyl, 4-(methylsulfinyl)phenyl, 4-(aminosulfonyl)phenyl, 4-(methylaminosulfonyl)phenyl, 4-(dimethylaminosulfonyl)phenyl, 4-(tert-butylaminosulfonyl)phenyl, tetrazol-5-ylphenyl, cyclohexyl, benzyl, 4-chlorobenzyl, phenethyl, benzyloxy, 4-fluorobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-tert-butylbenzyloxy, 4-trifluoromethylbenzyloxy, phenethyloxy, 2-thienyl, 2-thiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 6-fluoropyridin-3-yl, 5-fluoropyridin-2-yl, 6-chloropyridin-3-yl, 6-methylpyridin-3-yl, 2-pyrimidinyl, 5-tetrazolyl, piperidino, 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-&Dgr;2-oxazolin-2-yl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-&Dgr;2-1,2,4-oxadiazolin-3-yl, 5-oxo-&Dgr;2-1,2,4-thiadiazolin-3-yl, 2-oxo-3H-1,2,3,5-oxathiadiazolin-4-yl, 4-hydroxypiperidinomethyl, piperidinocarbonyl, 4-hydroxypiperidinocarbonyl, 3,4-dihydroxypiperidinocarbonyl, 1-piperazinylcarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl, 4-thiomorpholinylcarbonyl, phenoxy, 2,4-dichlorophenoxy, tetrahydropyranyloxy, 2-pyridylmethyloxy, 3-pyridylmethyloxy, 2-chloropyridin-4-ylmethyloxy, 4-pyridylmethyloxy, 2-piperidylmethyloxy, 3-piperidylmethyloxy, 4-piperidylmethyloxy, 1-methylpiperidin-4-ylmethyloxy, 1-acetylpiperidin-4-ylmethyloxy, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyloxy, 1-(methylsulfonyl)piperidin-4-ylmethyloxy, 2-methylthiazolin-4-yloxy, 2,4-dimethylthiazolin-5-yloxy, dimethylaminocarbonyl-methyloxy, piperidinocarbonylmethyloxy, 4-hydroxypiperidinocarbonylmethyloxy, 2-methylthiazol-4-yl, (2-methylthiazol-4-yl)methyloxy, (2,4-dimethylthiazol-5-yl)methyloxy, benzoyl, 3-fluorobenzoyl, 4-chlorobenzylamino, 3,5-dichlorobenzylamino, 4-trifluoromethylbenzylamino, 2-pyridylmethylamino, benzoylamino, 4-chlorobenzoylamino, 4-trifluoromethylbenzoylamino, 3,5-dichlorobenzoylamino, 3-nitro-4-methoxybenzoylamino, 4-nitro-3-methoxybenzoylamino, 3-pyridylcarbonylamino, morpholinocarbonyl-amino, 2-oxazolinylamino, 4-hydroxypiperidinosulfony, 4-methylphenylsulfonylamino, 2-thiazolylaminosulfonyl, 2-pyridylaminosulfonyl, benzylaminocarbonyl, N-benzyl-N-methylaminocarbonyl, (4-pyridylmethyl)aminocarbonyl or (cyclohexylmethyl)aminocarbonyl, 2-hydroxyethyloxy, 3-hydroxypropyloxy, 2-methoxyethoxy, 2-(2-methoxyethoxy)ethoxy, azetidinylcarbonyl, 3-hydroxypyrrolidinylcarbonyl, 3-hydroxypiperidinocarbonyl, 4-hydroxypiperidinocarbonyl, 3,4-dihydroxypiperidinocarbonyl, 4-methoxypiperidinocarbonyl, 4-carboxypiperidinocarbonyl, 4-(hydroxymethyl)piperidinocarbonyl, 2-oxopiperidinocarbonyl, 4-oxopiperidinocarbonyl, 2,6-dimethylpiperidinocarbonyl, 2,2,6,6-tetramethylpiperidinocarbonyl, 2,2,6,6-tetramethyl-4-hydroxypiperidinocarbonyl, 1-oxothiomorpholin-4-ylcarbonyl, 1,1-dioxothiomorpholin-4-ylcarbonyl, 1-(methylsulfonyl)piperidin-4-ylaminocarbonyl, 4-methylsulfonylpiperazinylcarbonyl, 4-methylpiperazinylcarbonyl, N,N-bis(2-hydroxyethyl)aminocarbonyl, phenylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclohexylaminocarbonyl, 4-hydroxycyclohexylaminocarbonyl, 4-methylthiazol-2-ylmethylaminocarbonyl, 2-(4-hydroxypiperidino)-ethyloxy, 2-pyridylmethylaminocarbonyl, 3-pyridylmethylamino-carbonyl, N-methyl-N-(4-pyridylmethyl)aminocarbonyl, cyclohexylmethyloxy, 4-hydroxypiperidinocarbonylmethyloxy and 4-methylthiazol-2-ylmethyloxy.

[1481] Particularly preferable examples of the substituent include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, hydroxymethyl, carboxyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylamino-carbonyl, (2-hydroxylethyl)aminocarbonyl, (carboxymethyl)-aminocarbonyl, methoxy, 2-isopentenyloxy, 2-propynyloxy, methylthio, methylamino, dimethylamino, acetylamino, methylsulfonylamino, methylsulfonyl, aminosulfonyl, dimethylaminosulfonyl, tert-butylaminosulfonyl, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 4-(methoxymethyl)phenyl, 4-(2-hydroxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, benzyl, phenethyl, benzyloxy, 4-fluorobenzyloxy, 4-chlorobenzyloxy, 2-thiazolyl, 3-pyridyl, 4-pyridyl, 4-pyridylmethyloxy, 2-piperidylmethyloxy, 3-piperidylmethyloxy, 4-piperidylmethyloxy, 1-methylpiperidin-4-ylmethyloxy, 1-acetylpiperidin-4-ylmethyloxy, 2-chloropiperidin-4-ylmethyloxy, 1-(methylsulfonyl)piperidin-4-ylmethyloxy, 2-methylthiazol-4-yl, (2-methylthiazol-4-yl)methyloxy, (2,4-dimethylthiazol-5-yl)methyloxy, 5-tetrazolyl, 3-fluorobenzoyl, piperidinocarbonyl, 4-hydroxylpiperidinocarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl, 4-thiomorpholinylcarbonyl, benzylaminocarbonyl, N-benzyl-N-methylaminocarbonyl, (4-pyridylmethyl)aminocarbonyl and (cyclohexylmethyl)aminocarbonyl.

[1482] Most preferable substituents are fluorine atom, chlorine atom, methyl, hydroxymethyl, carboxyl, carbamoyl, methylaminocarbonyl, dimethylaminocarbonyl, methoxy, methylamino, acetylamino, aminosulfonyl, dimethylaminosulfonyl, tert-butylaminosulfonyl, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl and 2-oxopyrrolidin-1-yl.

[1483] The w is preferably 1 or 2, r and t are preferably 0, 1 or 2, particularly preferably 0 or 1, more preferably 0, p is preferably 1, and q is preferably 0 or 2.

[1484] In formula [I], when X is 76

[1485] wherein each symbol is as defined above and w is 2 or above, one of Z is preferably C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D, particularly preferably C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.

[1486] The pharmaceutically acceptable salt may be any as long as it forms a non-toxic salt with a compound of the above-mentioned formula [I] or [II]. Such salt can be obtained by reacting the compound with an inorganic acid, such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and the like, or an organic acid, such as oxalic acid, malonic acid, citric acid, fumaric acid, lactid acid, malic acid, succinic acid, tartaric acid, acetic acid, trifluoroacetic acid, gluconic acid, ascorbic acid, methylsulfonic acid, benzylsulfonic acid and the like, or an inorganic base, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonium hydroxide and the like, or an organic base, such as methylamine, diethylamine, triethylamine, triethanolamine, ethylenediamine, tris(hydroxymethyl)methylamine, guanidine, choline, cinchonine and the like, with an amino acid, such as lysine, arginine, alanine and the like. The present invention encompasses water-retaining product, hydrate and solvate of each compound.

[1487] The compounds of the above-mentioned formula [I] or [II] have various isomers. For example, E compound and Z compound are present as geometric isomers, and when the compound has an asymmetric carbon, an enantiomer and a diastereomer are present due to the asymmetric carbon. A tautomer may be also present. The present invention encompasses all of these isomers and mixtures thereof.

[1488] The present invention also encompasses prodrug and metabolite of each compound.

[1489] A prodrug means a derivative of the compound of the present invention, which is capable of chemical or metabolic decomposition, which shows inherent efficacy by reverting to the original compound after administration to a body, and which includes salts and complexes without a covalent bond.

[1490] When the inventive compound is used as a pharmaceutical preparation, the inventive compound is generally admixed with pharmaceutically acceptable carriers, excipients, diluents, binders, disintegrators, stabilizers, preservatives, buffers, emulsifiers, aromatics, coloring agents, sweeteners, thickeners, correctives, solubilizers, and other additives such as water, vegetable oil, alcohol such as ethanol, benzyl alcohol and the like, polyethylene glycol, glycerol triacetate, gelatin, lactose, carbohydrate such as starch and the like, magnesium stearate, talc, lanolin, petrolatum and the like, and prepared into a dosage form of tablets, pills, powders, granules, suppositories, infections, eye drops, liquids, capsules, troches, aerosols, elixirs, suspensions, emulsions, syrups and the like, which can be administered systemically or topically and orally or parenterally.

[1491] While the dose varies depending on the age, body weight, general condition, treatment effect, administration route and the like, it is from 0.1 mg to 1 g for an adult per dose, which is given one to several times a day.

[1492] The prophylaxis of hepatitis C means, for example, administration of a pharmaceutical agent to an individual found to carry an HCV by a test and the like but without a symptom of hepatitis C, or to an individual who shows an improved disease state of hepatitis after a treatment of hepatitis C, but who still carries an HCV and is associated with a risk of recurrence of hepatitis.

[1493] Inasmuch as HCV is known to be a virus associated with many genetic mutations, a compound effective for many genotypes is one of the preferable modes. If a compound ensures high blood concentration when administered as a pharmaceutical agent to an animal infected with HCV, it is also one of the preferable modes. From these aspects, a compound having high inhibitory activity on both HCV type 1a and type 1b and high blood concentration, such as 2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, is particularly preferable.

[1494] The fused ring compound of the formula [I] or [II] of the present invention can be administered to mammals inclusive of human for the purpose of prevention or treatment of hepatitis C or inhibition of hepatitis C virus polymerase. The fused ring compound of the present invention can be also administered to mammals inclusive of human along with at least one pharmaceutical agent (hereinafter combination drug) selected from an antiviral agent other than the compound of the formula [I], an antiinflammatory agent and an immunostimulant for the purpose of prevention or treatment of hepatitis C or inhibition of hepatitis C virus polymerase. In the case of combined administration, the compound of the present invention can be administered simultaneously with the combination drug or administered at certain time intervals. In the case of combined administration, a pharmaceutical composition containing the compound of the present invention and a combination drug can be administered. Alternatively, a pharmaceutical composition containing the compound of the present invention and a pharmaceutical composition containing a combination drug may be administered separately. The administration route may be the same or different.

[1495] In the case of a combined administration, the compound of the present invention can be administered once a day or several times a day in a single dose of 0.1 mg to 1 g, or may be administered in a smaller dose. The combination drug can be administered in a dose generally used for the prevention or treatment of hepatitis C or in a smaller dose.

[1496] Examples of other antiviral agent include interferons (interferon &agr;, interferon &bgr;, interferon &ggr; etc.), Ribavirin (1-&bgr;-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) and the like.

[1497] Examples of the production method of the compound to be used for the practice of the present invention are given in the following. However, the production method of the compound of the present invention is not limited to these examples.

[1498] Even if no directly corresponding disclosure is found in the following Production Methods, the steps may be modified for efficient production of the compound, such as introduction of a protecting group into a functional group with deprotection in a subsequent step, and changing the order of Production Methods and steps.

[1499] The treatment after reaction in each step may be conventional ones, for which typical methods, such as isolation and purification, crystallization, recrystallization, silica gel chromatography, preparative HPLC and the like, can be appropriately selected and combined.

Production Method 1

[1500] In this Production Method, a benzimidazole compound is formed from a nitrobenzene compound.

[1501] Production Method 1-1 77

[1502] wherein Hal is halogen atom, such as chlorine atom, bromine atom and the like, Rc1 is halogen atom, such as chlorine atom, bromine atom and the like, or hydroxyl group, and other symbols are as defined above.

[1503] Step 1

[1504] A compound [1] obtained by a conventional method or a commercially available compound [1] is reacted with amine compound [2] in a solvent such as N,N-dimethylformamide (DMF), acetonitrile, tetrahydrofuran (THF), toluene and the like in the presence or absence of a base such as potassium carbonate, triethylamine, potassium t-butoxide and the like at room temperature or with heating to give compound [3].

[1505] Step 2

[1506] The compound [3] is hydrogenated in a solvent such as methanol, ethanol, THF, ethyl acetate, acetic acid, water and the like in the presence of a catalyst such as palladium carbon, palladium hydroxide, platinum oxide, Raney nickel and the like at room temperature or with heating to give compound [4]. In addition, compound [3] is reduced with a reducing agent such as zinc, iron, tin(II) chloride, sodium sulfite and the like, or reacted with hydrazine in the presence of iron(III) chloride to give compound [4].

[1507] Step 3

[1508] The compound [4] is condensed with carboxylic acid compound [5] in a solvent such as DMF, acetonitrile, THF, chloroform, ethyl acetate, methylene chloride, toluene and the like using a condensing agent such as dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, diphenylphosphoryl azide and the like and, where necessary, adding N-hydroxysuccinimide, 1-hydroxybenzotriazole and the like to give amide compound [6]. Alternatively, amide compound [6] can be obtained from compound [5] as follows. The carboxylic acid compound [5] is converted to an acid halide derived with thionyl chloride, oxalyl chloride and the like, or an active ester (e.g., mixed acid anhydride derived with ethyl chlorocarbonate and the like), which is then reacted in the presence of a base, such as triethylamine, potassium carbonate, pyridine and the like, or in an amine solvent, such as pyridine and the like, to give amide compound [6].

[1509] Step 4

[1510] The compound [6] is heated in a solvent such as ethanol, methanol, toluene, DMF, chloroform and the like or without a solvent in the presence of an acid such as acetic acid, formic acid, hydrochloric acid, dilute sulfuric acid, phosphoric acid, polyphosphoric acid, p-toluenesulfonic acid and the like, a halogenating agent such as zinc chloride, phosphorus oxychloride, thionyl chloride and the like or acid anhydride such as acetic anhydride and the like, to allow cyclization to give compound [I-2].

[1511] Production Method 1-2

[1512] This Production Method is an alternative method for producing compound [I-2]. 78

[1513] wherein each symbol is as defined above.

[1514] Step 1

[1515] The compound [3] obtained in the same manner as in Step 1 of Production Method 1-1 is subjected to amide condensation with compound [5] in the same manner as in Step 3 of Production Method 1-1 to give compound [7].

[1516] Step 2

[1517] The compound [7] is reduced in the same manner as in Step 2 of Production Method 1-1 to give compound [8].

[1518] Step 3

[1519] The compound [8] is subjected to cyclization in the same manner as in Step 4 of Production Method 1-1 to give compound [I-2].

[1520] Production Method 1-3 79

[1521] wherein Rc2 is alkyl such as methyl, ethyl and the like, and other symbols are as defined above.

[1522] The compound [4] is reacted with imidate compound [9] in a solvent such as methanol, ethanol, acetic acid, DMF, THF, chloroform and the like at room temperature or with heating to give compound [I-2].

[1523] In addition, compound [4] may be reacted with aldehyde compound [10] in a solvent such as acetic acid, formic acid, acetonitrile, DMF, nitrobenzene, toluene and the like in the presence or absence of an oxidizing agent such as benzofuroxan, manganese dioxide, 2,3-dichloro-5,6-dicyano-p-benzoquinone, iodine, potassium ferricyanide and the like with heating to give compound [I-2].

[1524] Alternatively, compound [4] and carboxylic acid compound [11] may be heated to allow reaction in the presence of polyphosphoric acid, phosphoric acid, phosphorus oxychloride, hydrochloric acid and the like to give compound [I-2].

Production Method 2

[1525] In this Production Method, conversion of the substituents (R1, R2, R3, R4) on the benzene ring of benzimidazole is shown. While a method of converting R2 when R1, R3 and R4 are hydrogen atoms is shown, this Production Method is applicable irrespective of the position of substitution.

[1526] Production Method 2-1

[1527] Conversion of carboxylic acid ester moiety to amide 80

[1528] wherein E is a single bond, —(CH2)5—, —O—(CH2)5— or —NH—(CH2)5— (wherein s is an integer of 1 to 6), Rc3, Rc4 and Rc5 are C1-6 alkyl, and other symbols are as defined above.

[1529] Step 1

[1530] The compound [I-2-1] obtained in the same manner as in the above-mentioned Production Method is subjected to hydrolysis in a solvent such as methanol, ethanol, THF, dioxane and the like, or in a mixed solvent of these solvents and water under basic conditions with sodium hydroxide, potassium hydroxide, potassium carbonate, lithium hydroxide and the like or under acidic conditions with hydrochloric acid, sulfuric acid and the like to give compound [I-2-2].

[1531] Step 2

[1532] The compound [I-2-2] is reacted with compound [12] in the same manner as in Step 3 of Production Method 1-1 to give compound [I-2-3].

[1533] Production Method 2-2

[1534] Conversion of cyano group to substituted amidino group 81

[1535] wherein each symbol is as defined above.

[1536] The compound [I-2-4] obtained in the same manner as in the above-mentioned Production Method is reacted with hydroxylamine in a solvent such as water, methanol, ethanol, THF, DMF and the like to give compound [I-2-5]. When a salt of hydroxylamine such as hydrochloride and the like is used, the reaction is carried out in the presence of a base such as sodium hydrogencarbonate, sodium hydroxide, triethylamine and the like.

[1537] Production Method 2-3

[1538] Conversion of sulfonic acid ester moiety to sulfonic acid 82

[1539] wherein Rc6 is C1-6 alkyl, and other symbols are as defined above.

[1540] The compound [I-2-6] obtained in the same manner as in the lo above-mentioned Production Method is reacted with iodide salt such as sodium iodide, lithium iodide and the like, bromide salt :such as sodium bromide, trimethylammonium bromide and the like, amine such as pyridine, trimethylamine, triazole and the like, phosphine such as triphenylphosphine and the like in a solvent such as DMF, dimethyl sulfoxide (DMSO), acetonitrile, methanol, ethanol, water and the like with heating to give compound [I-2-7].

Production Method 3

[1541] This Production Method relates to convertion of the substituent(s) on phenyl group at the 2-position of benzimidazole. This Production Method can be used even when phenyl is a different ring.

[1542] Production Method 3-1

[1543] Conversion of hydroxyl group to ether 83

[1544] wherein Rc7 is optionally substituted alkyl corresponding to Ra11, G1 is a single bond, *—(CH2)n—, *—(CH2)n—O—, *—(CH2)n—CO— or *—(CH2)m—CRa15Ra16)—(CH2)n—, wherein * show the side to be bonded to Rc1, and other symbols are as defined above.

[1545] When Rc1 of compound [13] is halogen atom, compound [I-2-8] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [13] in a solvent such as DMF, DMSO, acetonitrile, ethanol, THF and the like in the presence of a base such as sodium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium ethoxide, potassium t-butoxide and the like at room temperature or with heating to give compound [II-2-1].

[1546] When Rc1 of compound [13] is hydroxyl group, the hydroxyl group of compound [13] is converted to halogen atom with thionyl chloride, phosphorus tribromide, carbon tetrabromide-triphenylphosphine and the like and reacted with compound [I-2-8] by the aforementioned method to give compound [II-2-1]. In this case, compound [I-2-8] may be subjected to Mitsunobu reaction with compound [13] in a solvent such as DMF, acetonitrile, THF and the like using triphenylphosphine—diethyl azodicarboxylate and the like to give compound [II-2-1].

[1547] The compound [I-2-9] can be obtained in the same manner from compound [I-2-8] and compound [14].

[1548] Production Method 3-2

[1549] Conversion of nitro to substituted amino group 84

[1550] wherein Rc8 is C1-6 alkyl, G2 is *—(CH2)n— or *—CHRa15, G3 is —CO—, *—CO2—, *—CONH— or —SO2—, and other symbols are as defined above.

[1551] Step 1

[1552] The nitro compound [I-2-10] obtained in the same manner as in the above-mentioned Production Method is reacted in the same manner as in Step 2 of Production Method 1-1 to give compound [I-2-11].

[1553] Step 2

[1554] The compound [I-2-11] is alkylated with compound [15] in the same manner as in Production Method 3-1 to give compound [II-2-2].

[1555] Step 3

[1556] When G3 of compound [16] is —CO—, —CO2— or —CONH—, compound [I-2-11] is acylated with compound [16] in the same manner as in Step 3 of Production Method 1-1 to give compound [II-2-3].

[1557] When G3 of compound [16] is —SO2—, sulfonylation is conducted using sulfonyl halide instead of acid halide used in Step 3 of Production Method 1-1 to give compound [II-2-3].

[1558] The compound [I-2-11] is acylated with compound [17] in the same manner as above to give compound [I-2-12].

[1559] This Production Method is applied in the same manner as above to give disubstituted compounds (tertiary amine) of compound [II-2-2], compound [II-2-3] and compound [1-2-12].

[1560] Production Method 3-3

[1561] Conversion of carboxylic acid ester moiety to amide 85

[1562] wherein Rc9 is C1-6 alkyl, G4 is #—(CH2)n—, #—(CH2)n—NH— or #—CHRa14— wherein # shows the side that is bounded to amine and other symbols are as defined above.

[1563] Step 1

[1564] The compound [I-2-13] obtained in the same manner as in the above-mentioned Production Method is reacted in the same manner as in Step 1 of Production Method 2-1 to give compound [I-2-14].

[1565] Step 2

[1566] The compound [I-2-14] is reacted with compound [18] in the same manner as in Step 2 of Production Method 2-1 to give compound [II-2-4].

[1567] The compound [I-2-15] is obtained from compound [I-2-14] and compound [19] in the same manner as above.

Production Method 4

[1568] In this Production Method, additional substituent(s) is(are) introduced into ring B on phenyl group that substitutes the 2-position of benzimidazole. This Production Method is applicable even when phenyl is a different ring.

[1569] Production Method 4-1

[1570] Direct bonding of ring Z″ to ring B 86

[1571] wherein ring Z″—M is aryl metal compound, ring Z″ moiety is optionally substituted C6-14 aryl or optionally substituted heterocyclic group corresponding to substituent Z, and the metal moiety contains boron, zinc, tin, magnesium and the like, such as phenylboronic acid, w″ is 0, 1 or 2, and other symbols are as defined above.

[1572] The compound [II-2-5] obtained in the same manner as in the above-mentioned Production Method is reacted with aryl metal compound [20] in a solvent such as DMF, acetonitrile, 1,2-dimethoxyethane, THF, toluene, water and the like in the presence of a palladium catalyst such as tetrakis(triphenylphosphine)-palladium, bis(triphenylphosphine)palladium(II) dichloride, palladium acetate—triphenylphosphine and the like, a nickel catalyst such as nickel chloride, [1,3-bis(diphenylphosphino)-propane]nickel(II) chloride and the like, and a base such as potassium carbonate, potassium hydrogencarbonate, sodium hydrogen-carbonate, potassium phosphate, triethylamine and the like at room temperature or with heating, to give compound [II-2-6].

[1573] Production Method 4-2

[1574] Conversion of hydroxyl group to ether 87

[1575] wherein Rc10 is —Ra20 or —(CH2)p—CORa21 corresponding to substituent Z, and other symbols are as defined above.

[1576] The compound [II-2-7 ]obtained in the same manner as in the above-mentioned Production Method is reacted with compound [21] in the same manner as in Production Method 3-1 to give compound [II-2-8].

[1577] Production Method 4-3

[1578] Synthesis in advance of ring B part such as compound [13] in Production Method 3-1 88

[1579] wherein Rc11 is leaving group such as bromine atom, iodine atom, trifluoromethanesulfonyloxy and the like, Rc12 is formyl, carboxyl or carboxylic acid ester such as methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl and the like, and other symbols are as defined above.

[1580] Step 1

[1581] Commercially available compound [22] or compound [22] obtained by a conventional method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-1 to give compound [23].

[1582] Step 2

[1583] The compound [23] obtained in the same manner as in the above-mentioned Production Method is reduced according to a conventional method to give compound [24].

[1584] For example, compound [23] is reacted with in a solvent such as methanol, ethanol, THF and the like in the presence of a reducing agent such as lithium aluminum hydride, sodium borohydride and the like under cooling to heating to give compound [24].

[1585] Step 3

[1586] The compound [24] obtained in the same manner as in the above-mentioned Production Method is reacted in a solvent such as 1,4-dioxane, diethyl ether, THF, dichloromethane, chloroform, toluene and the like with a halogenating agent, such as phosphorus pentachloride, phosphorus tribromide, thionyl chloride and the like, in the presence of a tertiary amine such as pyridine and the like to give compound [25].

[1587] Step 4

[1588] The compound [24] or [25] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [I-2-8] in the same manner as in Production Method 3-1 to give compound [II-2-9].

[1589] Production Method 4-4 89

[1590] wherein M′ is a metal such as magnesium, lithium, zinc and the like, and other symbols are as defined above.

[1591] Step 1

[1592] Commercially available compound [41] or compound [41] obtained by a conventional method is converted to aryl metal reagent by a conventional method to give compound [42].

[1593] For example, when M′ is magnesium, magnesium is reacted with compound [41] in a solvent such as THF, diethyl ether, benzene, toluene and the like, preferably THF, from cooling to heating preferably at −100° C. to 100° C. to give compound [42].

[1594] Step 2

[1595] The compound [42] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [43] to give compound [44].

[1596] The compound [42] is reacted in a solvent such as diethyl ether, benzene, toluene, THF and the like, preferably THF, from cooling to room temperature, preferably at −100° C. to 30° C. to give compound [44].

[1597] step 3

[1598] The compound [44] obtained in the same manner as in the above-mentioned Production Method is halogenated in the same manner as in Step 3 of Production Method 4-3 to give compound [45].

[1599] The compound [44] is reacted with thionyl chloride and pyridine preferably in toluene solvent to give compound [45].

[1600] When compound [45] is symmetric, namely, when the ring B—(Z)w moiety and the ring B′—(Z′)w′ moiety are the same, compound [42] is reacted with formate such as methyl formate, ethyl formate and the like, preferably ethyl formate, in a solvent such as diethyl ether, benzene, toluene, THF and the like, preferably THF, from cooling to room temperature, preferably at −100° C. to 30° C., to give compound [45].

[1601] Production Method 4-5

[1602] Method including steps to introduce a protecting group into a functional group 90 91

[1603] wherein Rc13 is carboxylic acid protecting group such as tert-butyl and the like, Rc14 is carboxylic acid protecting group such as methyl and the like and other symbols are as defined above.

[1604] Step 1

[1605] Commercially available compound [26] or compound [26] obtained by a conventional method is protected by a conventional method to give compound [27].

[1606] For example, when Rc13 is tert-butyl, compound [26] is converted to acid halide with thionyl chloride, oxalyl chloride and the like in a solvent such as THF, chloroform, dichloromethane, toluene and the like, and reacted with potassium tert-butoxide to give compound [27].

[1607] As used herein, Rc13 may be a different protecting group as long as it is not removed during the Step 2 or Step 3 but removed in Step 4 without affecting —CO2Rc14.

[1608] Step 2

[1609] The methyl group of compound [27] obtained in the same manner as in the above-mentioned Production Method is converted to bromomethyl with N-bromosuccinimide and N,N′-azobisisobutyronitrile and reacted with compound [I-2-16] in the same manner as in Production Method 3-1 to give compound [II-2-10].

[1610] Step 3

[1611] The compound [II-2-10] obtained in the same manner as in the above-mentioned Production Method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-1 to give compound [II-2-11].

[1612] Step 4

[1613] The Rc13 of the compound [II-2-11] obtained in the same manner as in the above-mentioned Production Method is removed by a conventional method to give compound [II-2-12].

[1614] The protecting group of carboxylic acid can be removed by a conventional deprotection method according to the protecting group. In this Step, the conditions free from reaction of Rc14 are preferable. For example, when Rc13 is tert-butyl, compound [II-2-11] is treated with trifluoroacetic acid in a solvent such as dichloromethane, chloroform and the like to give compound [II-2-12].

[1615] Step 5

[1616] The compound [II-2-12] obtained in the same manner as in the above-mentioned Production Method is subjected to amide condensation with compound [28] in the same manner as in Step 3 of Production Method 1-1 to give compound [II-2-13].

[1617] Step 6

[1618] The compound [II-2-13] obtained in the same manner as in the above-mentioned Production Method is deprotected in the same manner as in Step 1 of Production Method 2-1 to give compound [II-2-14].

[1619] As used herein, Rc14 is preferably a protecting group that does not react during the Step 1 through Step 5 but removed in this Step.

[1620] For example, when Rc14 is methyl, compound [II-2-13] is reacted in an alcohol solvent such as methanol, ethanol, n-propanol, isopropanol and the like or a mixed solvent of alcohol solvent and water in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide and the like from cooling to heating for deprotection, followed by acidifying the reaction solution to give compound (II-2-14].

[1621] Production Method 4-6 92

[1622] wherein g is an integer of 1 to 5, and other sumbols are as defined above.

[1623] Step 1

[1624] The compound [I-2-16] obtained by the above-mentioned Production Method is reacted with toluene derivative [41] in the same manner as in Step 2 of Production Method 4-5 to give compound [II-2-17].

[1625] Step 2

[1626] The compound [II-2-17] obtained by the above-mentioned Production Method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-1 to give compound [II-2-18].

[1627] Step 3

[1628] The compound [II-2-18] obtained by the above-mentioned Production Method is reduced in the same manner as in Step 2 of Production Method 1-1 to give compound [II-2-19].

[1629] Step 4

[1630] The compound [II-2-19] obtained by the above-mentioned Production Method is amide condensed with compound [42] in the same manner as in Step 3 of Production Method 1-1 and subjected to cyclization in the same manner as in Step 1 of Production Method 1-1 to give compound [II-2-20].

[1631] Step 5

[1632] The compound [II-2-20] obtained by the above-mentioned Production Method is hydrolyzed in the same manner as in Step 1 of Production Method 2-1 to give compound [II-2-21].

Production Method 5

[1633] Formation of indole ring 93

[1634] wherein Rc15 is protecting group such as trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl and the like, and other symbols are as defined above.

[1635] Step 1

[1636] The compound [29] obtained in the same manner as in the above-mentioned Production Method or conventional method is reacted with compound [30] in a solvent such as DMF, acetonitrile, 1,2-dimethoxyethane, THF, toluene, water and the like using a palladium catalyst such as tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium(II) dichloride, palladium acetate—triphenylphosphine and the like, a copper catalyst such as copper(I) iodide and the like or a mixture thereof, and in the presence of a base such as potassium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate, potassium phosphate, triethylamine and the like to give compound [31].

[1637] Step 2

[1638] The compound [31] obtained in the same manner as in the above-mentioned Production Method is reacted in an alcohol solvent such as methanol, ethanol and the like or a mixed solvent of an alcohol solvent and a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, methylene chloride, toluene and the like in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydride, sodium hydride, potassium hydride and the like at room temperature or with heating for deprotection, and reacted with compound [32] obtained in the same manner as in Step 1 of Production Method 1-1 in the same manner as in Step 1 of Production Method 5 to give compound [33].

[1639] Step 3

[1640] The compound [33] obtained in the same manner as in the above-mentioned Production Method was subjected to cyclization in a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, methylene chloride, toluene and the like in the presence of a copper catalyst such as copper(I) iodide and the like or a palladium catalyst such as palladium(II) chloride and the like at room temperature or with heating to give compound [II-2-15].

Production Method 6

[1641] Formation of imidazo[1,2-a]pyridine ring 94

[1642] wherein Rc16 and Rc17 are each independently alkyl, such as methyl, ethyl and the like, and other symbols are as defined above.

[1643] Step 1

[1644] The compound [34] obtained by the above-mentioned Production Method or a conventional method is subjected to amide condensation with compound [35] in the same manner as in Step 3 of Production Method 1-1 to give compound [36].

[1645] Step 2

[1646] The compound [36] obtained by the above-mentioned Production Method is reacted with Grignard reagent [37] obtained by a conventional method to give compound [38].

[1647] Alternatively, an acid halide of compound [34] may be used instead of compound [36].

[1648] Step 3

[1649] The compound [38] obtained by the above-mentioned Production Method is subjected to halogenation by a conventional method to give compound [39].

[1650] For example, when Hal is a bromine atom, compound [38] is reacted with bromine under cooling or at room temperature in a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, toluene and the like to give compound [39].

[1651] Alternatively, a halogenating agent such as hypohalite (e.g., hypochlorite and the like), N-bromosuccinimide and the like may be used instead of bromine for halogenation.

[1652] Step 4

[1653] The compound [39] obtained by the above-mentioned Production Method is subjected to cyclization with compound [40] obtained by a conventional or known method (JP-A-8-48651) in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydride, sodium hydride, potassium hydride and the like in a solvent or without a solvent at room temperature or with heating to give compound [II-2-16].

[1654] In the compounds of the formulas [I] and [II], a desired heterocyclic group can be formed according to a method similar to the methods disclosed in known publications. Examples of such heterocyclic group and reference publications are recited in the following.

[1655] 5-oxo-&Dgr;2-1,2,4-oxadiazolin-3-yl (or 2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl), 5-oxo-&Dgr;2-1,2,4-thiadiazolin-3-yl (or 2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl), 2-oxo-&Dgr;3-1,2,3,5-oxathiadiazolin-4-yl (or 2-oxo-&Dgr;3-1,2,4-oxathiadiazol-4-yl): Journal of Medicinal Chemistry, 39(26), 5228-35, 1996,

[1656] 5-oxo-&Dgr;2-1,2,4-triazolin-3-yl: J Org Chem, 61(24), 8397-8401, 1996,

[1657] 1-oxo-&Dgr;3-1,2,3,5-thiatriazolin-4-yl: Liebigs Ann Chem, 1376, 1980,

[1658] 3-oxo-&Dgr;4-1,2,4-oxadiazolin-5-yl: EP145095,

[1659] 5-oxo-&Dgr;2-1,3,4-oxadiazolin-2-yl: J Org Chem, 20, 412, 1955,

[1660] 5-oxo-&Dgr;3-1,2,4-dioxazolin-3-yl: J Prakt Chem, 314, 145, 1972,

[1661] 3-oxo-&Dgr;4-1,2,4-thiadiazolin-5-yl: JP-A-61-275271,

[1662] 5-oxo-&Dgr;3-1,2,4-dithiazolin-3-yl: J Org Chem, 61(19), 6639-6645, 1996,

[1663] 2-oxo-&Dgr;4-1,3,4-dioxazolin-5-yl: J Org Chem, 39, 2472, 1974,

[1664] 2-oxo-&Dgr;4-1,3,4-oxathiazolin-5-yl: J Med Chem, 35(20), 3691-98, 1992,

[1665] 5-oxo-&Dgr;2-1,3,4-thiadiazolin-2-yl: J Prakt Chem, 332(1), 55, 1990,

[1666] 5-oxo-&Dgr;2-1,4,2-oxathiazolin-3-yl: J Org Chem, 31, 2417, 1966,

[1667] 2-oxo-&Dgr;4-1,3,4-dithiazolin-5-yl: Tetrahedron Lett, 23, 5453, 1982,

[1668] 2-oxo-&Dgr;4-1,3,2,4-dioxathiazolin-5-yl: Tetrahedron Lett, 319, 1968,

[1669] 3,5-dioxoisooxazolidin-4-yl: Helv Chim Acta, 1973, 48, 1965,

[1670] 2,5-dioxoimidazolidin-4-yl: Heterocycles, 43(1), 49-52, 1996,

[1671] 5-oxo-2-thioxoimidazolidin-4-yl: Heterocycles, 5, 391, 1983,

[1672] 2,4-dioxooxazolidin-5-yl: J Am Chem Soc, 73, 4752, 1951,

[1673] 4-oxo-2-thioxooxazolidin-5-yl: Chem Ber, 91, 300, 1958,

[1674] 2,4-dioxothiazolidin-5-yl: JP-A-57-123175,

[1675] 4-oxo-2-thioxothiazolidin-5-yl: Chem Pharm Bull, 30, 3563, 1982,

[1676] The Production Methods shown in the above-mentioned Production Methods 2 to 4 can be used for the synthesis of compounds other than benzimidazole of the formulas [I] and [II], such as compounds [II-2-15] and [II-2-16].

[1677] The compounds of the formulas [I], [II] and [III], 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and 4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole and production methods thereof of the present invention are explained in detail in the following by way of Examples. It is needless to say that the present invention is not limited by these Examples.

EXAMPLE 1

Production of Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1678] Step 1: Production of Ethyl 4-chloro-3-nitrobenzoate

[1679] 4-Chloro-3-nitrobenzoic acid (300 g) was dissolved in ethyl alcohol (1500 ml) and concentrated sulfuric acid (100 ml) was added with ice-cooling. The mixture was refluxed under heating for 7 hr. The reaction mixture was poured into ice-cold water and the precipitated crystals were collected by filtration to give the title compound (332 g, yield 97%).

[1680] 1H-NMR (300 MHz, CDCl3): 8.50(1H, d, J=2.1 Hz), 8.16(1H, dd, J=8.4, 2.1 Hz), 7.63(1H, d, J=8.4 Hz), 4.43(2H, q, J=7.5 Hz), 1.42(3H, t, J=7.5 Hz)

[1681] Step 2: Production of Ethyl 4-cyclohexylamino-3-nitrobenzoate

[1682] Ethyl 4-chloro-3-nitrobenzoate (330 g) obtained in the previous step was dissolved in acetonitrile (1500 ml), and cyclohexylamine (220 g) and triethylamine (195 g) were added. The mixture was refluxed under heating overnight. The reaction mixture was poured into ice-cold water and the precipitated crystals were collected by filtration to give the title compound (400 g, yield 94%).

[1683] 1H-NMR (300 MHz, CDCl3): 8.87(1H, d, J=2.1 Hz), 8.35-8.46(1H, m), 8.02(1H, dd, J=9.1, 2.1 Hz), 6.87(1H, d, J=9.1 Hz), 4.35(2H, q, J=7.1 Hz), 3.65-3.50(1H, m), 2.14-1.29(10H, m), 1.38(3H, t, J=7.1 Hz)

[1684] Step 3: Production of Ethyl 3-amino-4-cyclohexylaminobenzoate

[1685] Ethyl 4-cyclohexylamino-3-nitrobenzoate (400 g) obtained in the previous step was dissolved in ethyl acetate (1500 ml) and ethyl alcohol (500 ml), and 7.5% palladium carbon (50% wet, 40 g) was added. The mixture was hydrogenated for 7 hr at atmospheric pressure. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. Diisopropyl ether was added to the residue and the precipitated crystals were collected by filtration to give the title compound (289 g, yield 80%).

[1686] 1H-NMR (300 MHz, CDCl3): 7.57(1H, dd, J=8.4, 1.9 Hz), 7.41(1H, d, J=1.9 Hz), 6.59(1H, d, J=8.4 Hz), 4.30(2H, q, J=7.1 Hz), 3.40-3.30(1H, m), 2.18-2.02(2H, m), 1.88-1.15(8H, m), 1.35(3H, t, J=7.1 Hz)

[1687] Step 4: Production of Ethyl 3-[4-(3-bromophenoxy)benzoyl]amino-4-cyclohexylaminobenzoate

[1688] 4-(3-Bromophenoxy)benzoic acid (74 g) was dissolved in chloroform (500 ml), and oxalyl chloride (33 ml) and dimethylformamide (catalytic amount) were added. The mixture was stirred for 4 hr at room temperature. The reaction mixture was concentrated under reduced pressure and dissolved in ,dichloromethane (150 ml). The resulting solution was added dropwise to a solution of ethyl 3-amino-4-cyclohexylaminobenzoate (66 g) obtained in the previous step in dichloromethane (500 ml) and triethylamine (71 ml), and the mixture was stirred for 1 hr at room temperature. The reaction mixture was poured into water and extracted with dichloromethane. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Diethyl ether was added to the residue for crystallization and the crystals were collected by filtration to give the title compound (129 g, yield 95%).

[1689] 1H-NMR (300 MHz, CDCl3): 8.00-7.78(4H, m), 7.66(1H, brs), 7.37-7.18(3H, m), 7.13-6.59(3H, m), 6.72(1H, d, J=8.7 Hz), 4.50(1H, brs), 4.29(2H, q, J=7.2 Hz), 3.36(1H, m), 2.12-1.96(2H, m), 1, 83-1.56(3H, m), 1.47-1.12(5H, m), 1.37(3H, t, J=7.2 Hz)

[1690] Step 5: Production of Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1691] Ethyl 3-[4-(3-bromophenoxy)benzoyl]amino-4-cyclohexylaminobenzoate (129 g) obtained in the previous step was suspended in acetic acid (600 ml) and the resulting suspension was refluxed under heating for 3 hr. The reaction mixture was concentrated under reduced pressure. Water was added to the residue and the precipitated crystals were collected by filtration to give the title compound (124 g, yield 99%).

[1692] 1H-NMR (300 MHz, CDCl3): 8.51(1H, d, J=1.5 Hz), 8.00(1H, dd, J=8.4, 1.5 Hz), 7.67(1H, d, J=8.4 Hz), 7.63(2H, d, J=8.7 Hz), 7.35-7.21(3H, m), 7.17(2H, d, J=8.7 Hz), 7.14(1H, m), 4.42(2H, q, J=7.2 Hz), 4.38(1H, m), 2.43-2.22(2H, m), 2.07-1.87(4H, m), 1.80(1H, m), 1.42(3H, t, J=7.2 Hz), 1.40-1.27(3H, m)

EXAMPLE 2

Production of 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid

[1693] Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylate (1.0 g) obtained in Example 1 was dissolved in tetrahydrofuran (10 ml) and ethyl alcohol (10 ml), and 4N sodium hydroxide (10 ml) was added. The mixture was refluxed under heating for 1 hr. The reaction mixture was concentrated under reduced pressure and water was added to the residue. The mixture was acidified with 6N hydrochloric acid and the precipitated crystals were collected by filtration to give the title compound (0.9 g, yield 96%). melting point: 255-256° C. FAB-Ms: 491(MH+)

[1694] 1H-NMR (300 MHz, DMSO-d6): (12.75(1H, brs), 8.24(1H, s), 7.96(1H, d, J=8.7 Hz), 7.86(1H, d, J=8.7 Hz), 7.71(2H, d, J=8.6 Hz), 7.47-7.34(3H, m), 7.24(2H, d, J=8.6 Hz), 7.20(1H, m), 4.31(1H, m), 2.38-2.18(2H, m), 2.02-1.79(4H, m), 1.65(1H, m), 1.44-1.20(3H, m)

EXAMPLE 3

Production of Ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate

[1695] Ethyl 3-amino-4-cyclohexylaminobenzoate (130 g) obtained in Example 1, Step 3, and methyl 4-hydroxybenzimidate hydrochloride (139 g) were added to methyl alcohol (1500 ml), and the mixture was refluxed under heating for 4 hr. The reaction mixture was allowed to cool and the precipitated crystals were collected by filtration to give the title compound (131 g, yield 72%).

[1696] 1H-NMR (300 MHz, CDCl3): 10.02(1H, brs), 8.21(1H, d, J=1.4 Hz), 7.93(1H, d, J=8.6 Hz), 7.83(1H, dd, J=8.6, 1.4 Hz), 7.48(2H, d, J=8.6 Hz), 6.95(2H, d, J=8.6 Hz), 4.39-4.25(1H, m), 4.33(1H, q, J=7.0 Hz), 2.35-2.18(2H, m), 1.98-1.79(4H, m), 1.70-1.60(1H, m), 1.46-1.19(3H, m), 1.35(3H, t, J=7.0 Hz)

EXAMPLE 4

Production of Ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1697] 2-Bromo-5-chlorobenzyl bromide prepared from 2-bromo-5-chlorotoluene (50 g), N-bromosuccinimide and N,N′-azobisisobutyronitrile, and ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (50 g) obtained in Example 3 were suspended in dimethylformamide (300 ml). Potassium carbonate (38 g) was added and the mixture was stirred for 1 hr at 80° C. with heating. The reaction mixture was allowed to cool and then added to a mixed solvent of water-ethyl acetate. The precipitated crystals were collected by filtration to give the title compound (50 g, yield 64%).

[1698] 1H-NMR (300 MHz, CDCl3): 8.50(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.4 Hz), 7.70-7.57(5H, m), 7.20(1H, dd, J=8.4, 2.5 Hz), 7.14(2H, d, J=8.7 Hz), 5.17(2H, s), 4.46-4.30(1H, m), 4.41(2H, q, J=7.1 Hz), 2.40-2.20(2H, m), 2.02-1.21(8H, m), 1.42(3H, t, J=7.1 Hz)

EXAMPLE 5

Production of Ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1699] Ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (49 g) obtained in Example 4,4-chlorophenylboronic acid (18 g) and tetrakis-(triphenylphosphine)palladium (10 g) were suspended in 1,2-dimethoxyethane (600 ml). Saturated aqueous sodium hydrogencarbonate solution (300 ml) was added and the mixture was refluxed under-heating for 2 hr. Chloroform was added to the reaction mixture. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, chloroform:ethyl acetate=97:3). Ethyl acetate and diisopropyl ether were added to the resulting oil for crystallization and the * resulting crystals were collected by filtration to give the title compound (44 g, yield 85%).

[1700] 1H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.6 Hz), 7.70-7.60(2H, m), 7.55(2H, d, J=8.7 Hz), 4.95(2H, s), 4.48-4.28(1H, m), 4.40(2H, m), 2.02-1.20(8H, m), 1.41(3H, t, J=7.1 Hz)

EXAMPLE 6

Production of 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1701] Ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (43 g) obtained in Example 5 was treated in the same manner as in Example 2 to give the title compound (33 g, yield 76%).

[1702] melting point: 243-244° C. FAB-Ms: 571(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.32(1H, s), 8.28(1H, d, J=8.9 Hz), 8.05(1H, d, J=8.8 Hz), 7.76-7.72(3H, m), 7.58-7.46(5H, m), 7.40(1H, d, J=8.3 Hz), 7.24(2H, d, J=8.9 Hz), 5.11(2H, s), 4.36(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m)

EXAMPLE 7

Production of Ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1703] Ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate obtained in Example 3 and 2-bromo-5-methoxybenzyl bromide were treated in the same manner as in Example 4 to give the title compound (59 g).

EXAMPLE 8

Production of Ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy[-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1704] Ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate obtained in Example 7 was treated in the same manner as in Example 5 to give the title compound (48 g, yield 77%).

[1705] 1H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.4 Hz), 7.64(1H, d, J=8.6 Hz), 7.54(2H, d, J=8.7 Hz), 7.37(2H, d, J=8.6 Hz), 7.31(2H, d, J=8.6 Hz), 7.25(1H, d, J=8.4 Hz), 7.19(1H, d, J=2.7 Hz), 7.00(2H, d, J=8.7 Hz), 6.97(1H, dd, J=8.4, 2.7 Hz), 4.98(2H, s), 4.41(2H, q, J=7.1 Hz), 4.42-4.29(1H, m), 3.88(3H, s), 2.40-2.20(2H, m), 2.01-1.88(4H, m), 1.83-1.73(1H, m), 1.42(3H, t, J=7.1 Hz), 1.41-1.25(3H, m)

EXAMPLE 9

Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1706] Ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (52 g) obtained in Example 8 was treated in the same manner as in Example 2 to give the title compound (44 g, yield 89%).

[1707] melting point: 248-249° C. FAB-Ms: 568(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.20(1H, s), 7.88(1H, d, J=8.7 Hz), 7.85(1H, d, J=8.7 Hz), 7.57(d, 2H, J=8.6 Hz), 7.46(2H, d, J=8.6 Hz), 7.44(2H, d, J=8.6 Hz), 7.29(1H, d, J=8.5 Hz), 7.24(1H, d, J=2.6 Hz), 7.11(2H, d, J=8.6 Hz), 7.06(1H, dd, J=8.5, 2.6 Hz), 5.04(2H, s), 4.26(1H, m), 3.83(3H, s), 2.38-2.29(2H, m)

EXAMPLE 10

Production of Ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylate

[1708] Ethyl 3-amino-4-cyclohexylaminobenzoate (500 mg) obtained in Example 1, Step 3, was dissolved in methyl alcohol (6 ml) and trans-4-stilbenecarbaldehyde (397 mg) was added under ice-cooling. The mixture was stirred overnight at room temperature. The reaction mixture was ice-cooled and benzofuroxan (259 mg) dissolved in acetonitrile (2 ml) was. added. The mixture was stirred for 7 hr at 50° C., The reaction mixture was ice-cooled. After 1N sodium-hydroxide was added, ethyl acetate was added and the mixture was extracted. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=4:1) to give the title compound (540 mg, yield 63%).

[1709] 1H-NMR (300 MHz, DMSO-d6): 8.28(1H d, J=1.4 Hz), 8.01(1H, d, J=8.7 Hz) 7.90-7.80(3H, m), 7.75-7.65(4H, m), 7.50-7.25(5H, m), 4.35(2H, q, J=7.0 Hz), 4.31(1H, m), 2.40-2.20(2H, m), 2.00-1.80(4H, m), 1.63(1H, m), 1.40-1.20(3H, m), 1.36(3H, t, J=7.0 Hz)

EXAMPLE 11

Production of 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylic-acid

[1710] Ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylate (127 mg) obtained in Example 10 was treated in the same manner as in Example 2 to give the title compound (116 mg, yield 97%).

[1711] melting point: not lower than 300° C. FAB-Ms: 423(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.25(1H, s), 7.96-7.29(13H, m), 4.33(1H, brt), 2.41-2.23(2H, m), 2.03-1.78(4H, m), 1.71-1.59(1H, m), 1.49-1.20(3H, m)

EXAMPLE 12

Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid

[1712] In the same manner as in Examples 1 and 2, the title compound (700 mg) was obtained.

[1713] FAB-Ms: 413(MH+) 1H-NMR (300 MHz, CDCl3): 8.60(1H, s), 8.04(1H, d, J=9.0 Hz), 7.63(2H, d, J=8.4 Hz), 7.51-7.32(6H, m), 7.14(2H, d, J=9.0 Hz), 5.16(2H, s), 5.03-4.89(1H, m), 2.41-1.63(8H, m)

EXAMPLE 13

Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide

[1714] 2-(4-Benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (700 mg) obtained in Example 12 was dissolved in dimethylformamide (10 ml), and ammonium chloride (108 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (390 mg), 1-hydroxybenzotriazole (275 mg) and triethylamine (0.3 ml) were added. The mixture was stirred overnight at room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Ethyl acetate and diisopropyl ether were added to the residue for crystallization and the crystals were collected by filtration to give the title compound (571 mg, yield 81%).

[1715] melting point: 232-233° C. FAB-Ms: 412(MH+) 1H-NMR (300 MHz, CDCl3): 8.23(1H, d, J=1.5 Hz), 7.86(1H, dd, J=8.5, 1.5 Hz), 7.65-7.30(8H, m), 7.13(2H, d, J=8.8 Hz), 5.16(2H, s), 4.93(1H, quint, J=8.8 Hz), 2.40-1.60(8H, m)

EXAMPLE 14

Production of 2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole

[1716] In the same manner as in Example 1, the title compound (400 mg) was obtained.

[1717] FAB-Ms: 394(MH+) 1H-NMR (300 MHz, CDCl3): 8.11(1H, s), 7.68-7.30(9H, m), 7.13(2H, s), 5.16(2H, s), 4.94(1H, quint, J=8.9 Hz), 2.35-1.60(8H, m)

EXAMPLE 15

Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime

[1718] 2-(4-Benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole (400 mg) obtained in Example 14 was suspended in ethyl alcohol (3 ml) and water (1.5 ml), and hydroxylamine hydrochloride (141 mg) and sodium hydrogencarbonate (170 mg) were added. The mixture was refluxed under heating overnight. The reaction mixture was allowed to cool and the precipitated crystals were collected by filtration to give the title compound (312 mg, yield 71%).

[1719] melting point: 225-226° C. FAB-Ms: 456(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.20(1H, s), 7.50-7.31(9H, m), 7.12(2H, d, J=8.7 Hz), 5.15(2H, s), 4.94(1H, quint, J=8.7 Hz), 3.61(3H, s), 3.40(3H, s), 2.41-1.42(8H, m)

EXAMPLE 16

Production of Ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxyl]phenyl}benzimidazole-5-carboxylate

[1720] Step 1: Production of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole

[1721] Ethyl 4-(4-fluorophenyl)-2-methyl-5-thiazolecarboxylate (59 g) prepared by a known method (Chem. Pharm. Bull., 43(6), 947, 1995) was dissolved in tetrahydrofuran (700 ml). Lithium aluminum hydride (13 g) was added under ice-cooling and the mixture was stirred for 30 min. Water (13 ml), 15% sodium hydroxide (13 ml) and water (39 ml) were added successively to the reaction mixture, and the precipitated insoluble materials were filtered off. The filtrate was concentrated under reduced pressure to give the title compound (37 g, yield 71%).

[1722] 1H-NMR (300 MHz, CDCl3): 7.60(2H, dd, J=8.7, 6.6 Hz), 7.11(2H, t, J=8.7 Hz), 4.80(2H, s), 2.70(3H, s)

[1723] Step 2: Production of 5-chloromethyl-4-(4-fluorophenyl)-2-methylthiazole,

[1724] 4-(4-Fluorophenyl)-5-hydroxymethyl-2-methylthiazole (37 g) obtained in the previous step was dissolved in chloroform (500 ml), and thionyl chloride (24 ml) and pyridine (2 ml) were added. The mixture was stirred for 3 hr at room temperature. The reaction mixture was poured into ice-cold water. The mixture was extracted with chloroform, and washed with water and saturated brine. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure to give the title compound (29 g, yield 76%).

[1725] 1H-NMR (300 MHz, CDCl3): 7.67(2H, dd, J=8.8, 5.4 Hz), 7.16(2H, t, J=8.7 Hz), 4.79(2H, s), 2.73(3H, s)

[1726] Step 3: Production of Ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate

[1727] 5-Chloromethyl-4-(4-fluorophenyl)-2-methylthiazole (28 g) obtained in the previous step and ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (36 g) obtained in Example 3 were treated in the same manner as in Example 4 to give the title compound (61 g, yield 100%).

[1728] APCI-Ms: 570(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.25(1H, d, J=1.5 Hz), 7.97(1H, d, J=8.7 Hz), 7.86(1H, dd, J=8.6, 1.6 Hz), 7.74(2H, dd, J=8.8, 5.5 Hz), 7.62(2H, d, J=8.7 Hz), 7.33(2H, t, J=8.9 Hz), 7.22(2H, t, J=8.9 Hz), 5.41(2H, s), 4.34(2H, q, J=7.1 Hz), 4.31(1H, m), 2.71(3H, s), 2.40-2.15(2H, m), 2.05-1.75(4H, m), 1.55-1.15(3H, m), 1.36(3H, t, J=7.1 Hz)

EXAMPLE 17

Production of 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid

[1729] Ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate (60 g) obtained in Example 16 was treated in the same manner as in Example 2 to give the title compound (39 g, yield 69%).

[1730] melting point: 196-198° C. FAB-Ms: 542(MH+) 1H-NMR (300 MHz, DMSO-d6): 13.1(1H, brs), 8.34(1H, s), 8.29(1H, d, J=8.8 Hz), 8.06(1H, d, J=8.7 Hz), 7.80-7.72(4H, m), 7.36-7.31(4H, m), 5.46(2H, s), 4.38(1H, m), 2.72(3H, s), 2.45-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.20(3H, m)

EXAMPLE 18

Production of Ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)-benzimidazole-5-carboxylate

[1731] In the same manner as in Example 3, the title compound (50 g) was obtained.

EXAMPLE 19

Production of Ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1732] Step 1: Production of 3,3′-difluorobenzhydrol

[1733] To a stirred solution of magnesium strip (35.4 g) in THF (200 ml), iodine strip was added and the mixture was heated with stirring under nitrogen stream until most of color of iodine was disappeared. A solution of 3-fluoro-bromobenzene (250.0 g) in THF (1000 ml) was added dropwise over 2.5 hr while the temperature of the solution was maintained at 60° C., After the completion of the addition of the solution, the resulting mixture was refluxed for 1 hr with heating. The resulting Grignard solution was ice-cooled and a solution of ethyl formate (63.2 g) in THF (200 ml) was added dropwise over 1 hr. After a stirring of the reaction solution for an additional 30 min, saturated aqueous ammonium chloride solution (700 ml) was added dropwise with ice-cooling and water (300 ml) was added. The mixture was stirred for 10 min. The organic layer and water layer were separated. Water layer was extracted with ethyl acetate, and the combined organic layer was washed with 2N hydrochloric acid, saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated off under reduced pressure to give the title compound (156.2 g, yield 99%).

[1734] 1H-NMR (300 MHz, CDCl3): 7.31(2H, td, J=7.9, 5.8 Hz), 7.15-7.80(4H, m), 6.97-6.94(2H, m), 5.82(1H, d, J=3.3 Hz), 2.30(1H, d, J=3.3 Hz)

[1735] Step 2: Production of 3,3′-difluorobenzhydryl chloride

[1736] To a solution of 3,3′-difluorobenzhydrol (150.0 g) obtained in the previous step in toluene (400 ml), pyridine (539 mg) was added at room temperature. To the solution, thionyl chloride (89.1 g) was added dropwise over 1 hr at room temperature and the resulting solution was stirred for an additional 2 hr. The solution was heated so that the temperature of the solution was at 40° C., and then stirred for an additional 1.5 hr. Thionyl chloride (8.1 g) was added again and the mixture was stirred for 30 min. To the reaction mixture, water was added. The organic layer was separated, and washed with water, saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was evaporated off under reduced pressure to give the title compound (158.2 g, yield 97%).

[1737] 1H-NMR (300 MHz, CDCl3): 7.32(2H, td, J=8.0, 5.9 Hz), 7.18-7.10(4H, m), 7.01(2H, tdd, J=8.2, 2.5, 1.2 Hz), 6.05(1H, s)

[1738] Step 3: Production of Ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1739] Ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)-benzimidazole-5-carboxylate (50 g) obtained in Example 18 and 3,3′-difluorobenzhydryl chloride (34 g) obtained in the previous step were treated in the same manner as in Example 4 to give the title compound (76 g, yield 99%).

[1740] FAB-Ms: 585(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.24(1H, d, J=1.4 Hz), 7.98(1H, d, J=8.7 Hz), 7.88(1H, d, J=8.7 Hz), 7.56(1H, t, J=8.6 Hz), 7.50-7.40(6H, m), 6.82(1H, s), 4.34(2H, q; J=7.1 Hz), 3.95(1H, m), 2.20-2.10(2H, m), 1.90-1.80(4H, m), 1.6(1H, m), 1.35(3H, t, J=7.2 Hz), 1.30-1.20(3H, mz)

EXAMPLE 20

Production of 2-{4-(bis[3-fluorophenyl]methoxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1741] Ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (75 g) obtained in Example 19 was treated in the same manner as in Example 2 to give the title compound (48 g, yield 62%).

[1742] melting point: 242-243° C. FAB-Ms: 557(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.29(1H, s), 8.16(1H, d, J=8.8 Hz), 7.99(1H, d, J=8.7 Hz), 7.66(1H, t, J=8.7 Hz), 7.51-7.40(6H, m), 7.30(1H, d, J=12.1 Hz), 7.20-7.14(3H, m), 6.88(1H, s), 4.07(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m)

EXAMPLE 21

Production of Ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate

[1743] In the same manner as in Example 1, the title compound (12 g) was obtained.

EXAMPLE 22

Production of Ethyl 2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate

[1744] Ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate (12 g) obtained in Example 21 was dissolved in tetrahydrofuran (200 ml) and ethyl alcohol (50 ml), 7.5% palladium carbon (50% wet, 1 g) was added. The mixture was hydrogenated for 1 hr at atmospheric pressure. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. Tetrahydrofuran was added to the residue to allow crystallization and the crystals were collected by filtration to give the title compound (11 g, yield 98%).

[1745] 1H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.3 Hz), 7.95(1H, dd, J=8.5, 1.3 Hz), 7.50-7.40(3H, m), 6.79(2H, d, J=4.6 Hz), 4.97(1H, quint, J=8.9 Hz), 4.40(2H, q; J=7.1 Hz), 3.74(2H, brs), 2.40-1.60(8H, m), 1.41(3H, t, J=7.1 Hz)

EXAMPLE 23

Production of Ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate

[1746] Ethyl 1-cyclopentyl-2-(4-aminophenyl)benzimidazole-5-carboxylate (300 mg) obtained in,Example 22 was dissolved in pyridine (3 ml) and chloroform (3 ml), and benzoyl chloride (127 mg) was added. The mixture was stirred for 30 min at room temperature. The reaction mixture was concentrated under reduced pressure and water was added to the residue to allow crystallization. The crystals were collected by filtration to give the title compound (403 mg; yield 100%).

[1747] 1H-NMR (300 MHz, CDCl3): 8.58(1H, s), 8.00(1H, d, J=9.0 Hz), 7.84(2H, d, J=7.5 Hz), 7.60-7.40(6H, m), 7.14(2H, d, J=7.5 Hz), 4.84(1H, quint, J=8.7 Hz), 4.41(2H, q, J=7.5 Hz), 2.20-1.30(8H, m), 1.41(3H, t, J=7.5 Hz)

EXAMPLE 24

Production of 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid

[1748] Ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (200 mg) obtained in Example 23 was treated in the same manner as in Example 2 to give the title compound (131 mg, yield 70%).

[1749] melting point: not lower than 300° C. FAB-Ms: 426(MH+) 1H-NMR (300 MHz, DMSO-d6): 10.75(1H, s), 8.35(1H, s), 8.15 and 7.85(4H, ABq, J=8.9 Hz), 8.10-7.98(4H, m), 7.70-7.55(3H, m), 5.02(1H, quint, J=8.7 Hz), 2.36-2.15(4H, m), 2.14-1.95(2H, m), 1.80-1.62(2H, m)

EXAMPLE 25

Production of Ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1750] Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (65 g) obtained in Example 1 and 3-chlorophenylboronic acid (23 g) were treated in the same manner as in Example 5 to give the title compound (59 g, yield 85%).

[1751] 1H-NMR (300 MHz, CDCl3): 8.51(1H, d, J=1.8 Hz), 7.99(1H, dd, J=8.7, 1.8 Hz), 7.71-7.55(4H, m), 7.51-7.43(2H, m), 7.43-7.27(4H, m), 7.19(1H, d, J=8.4 Hz), 7.12(1H, m), 4.41(2H, q, J=7.2 Hz), 4.39(1H, m), 2.42-2.22(2H, m), 2.03-1.87(4H, m), 1.79(1H, m), 1.42(3H, t, J=7.2 Hz), 1.39-1.29(3H, m)

EXAMPLE 26

Production of 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1752] Ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (59 g) obtained in Example 25 was treated in the same manner as in Example 2 to give the title compound (43 g, yield 76%).

[1753] melting point: 253-254° C. FAB-Ms: 523(MH+) 1H-NMR (300 MHz, DMSO-d6): 12.82(1H, brs), 8.24(1H, d, J=1.3 Hz), 7.98(1H, d, J=8.7 Hz), 7.89(1H, dd, J=8.7, 1.3 Hz), 7.78(1H, s), 7.72(2H, d, J=9.7 Hz), 7.70(1H, m), 7.64-7.42(5H, m), 7.25(2H, d, J=8.7 Hz), 7.20(1H, m), 4.33(1H, m), 2.39-2.17(2H, m), 2.00-1.76(4H, m), 1.65(1H, m), 1.50-1.22(3H, m)

EXAMPLE 27

Production of Ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1754] In the same manner as in Example 1, the title compound (87 g) was obtained.

EXAMPLE 28

Production of Ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)-phenyl]benzimidazole-5-carboxylate

[1755] Ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (87 g) obtained in Example 27 was dissolved in methyl alcohol (250 ml) and tetrahydrofuran (250 ml), and potassium carbonate (31 g) was added. The mixture was stirred for 30 min at room temperature. The insoluble materials were filtered off and the filtrate was concentrated under reduced pressure. Water was added to the residue and the mixture was neutralized with 2N hydrochloric acid. The precipitated crystals were collected by filtration to give the title compound (78 g, yield 97%).

[1756] 1H-NMR (300 MHz, DMSO-d6): 9.71(1H, s), 7.98(1H, d, J=8.7 Hz), 7.87(1H, d, J=8.7 Hz), 7.68(2H, d, J=8.6 Hz), 7.24(1H, t, J=8.1 Hz), 7.18(2H, d, J=8.6 Hz), 6.63(1H, d, J=8.1 Hz), 6.57(1H, d, J=8.1 Hz), 6.51(1H, s), 4.38-4.23(1H; m), 4.35(2H, q, J=6.9 Hz), 2.36-2.18(2H, m), 1.99-1.78(4H, m), 1.71-1.59(1H, m), 1.45-1.20(3H, m), 1.36(3H, t, J=6.9 Hz)

EXAMPLE 29

Production of Ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)-phenyloxy]phenyl}benzimidazole-5-carboxylate

[1757] Ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate (78 g) obtained in Example 28 was suspended in dimethylformamide (800 ml), and sodium hydride (60% oil, 14 g) was added under ice-cooling. The mixture was stirred for 1 hr at room temperature. After the reaction mixture was ice-cooled, 4-chloromethylpyridine hydrochloride (29 g) was added and the mixture was stirred for 30 min. The mixture was then stirred overnight at room temperature. Water was added to the reaction mixture and the precipitated crystals were collected by filtration. The resulting crystals were recrystallized from ethyl alcohol to give the title compound (77 g, yield 82%).

[1758] 1H-NMR (300 MHz, CDCl3): 8.63(2H, d, J=6.0 Hz), 8.51 (1H, s), 7.99(1H, d, J=8.7 Hz), 7.66(2H, d, J=8.7 Hz), 7.62(2H, d, J=8.7 Hz), 7.36(2H, d, J=8.7 Hz), 7.31(1H, t, J=8.2 Hz), 7.26(1H, s), 7.16(2H, d, J=8.7 Hz), 6.79-6.70(3H, m), 5.09(2H, s), 4.47-4.31(1H, m), 4.42(2H, q, J=7.0 Hz), 2.42-2.22(2H, m), 2.04-1.71(5H, m), 1.45-1.25(3H, m), 1.42(3H, t, J=7.0 Hz)

EXAMPLE 30

Production of 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]-phenyl}benzimidazole-5-carboxylic acid

[1759] Ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]-phenyl}benzimidazole-5-carboxylate (60 g) obtained in Example 29 was treated in the same manner as in Example 2 to give the title compound (54 g, yield 75%).

[1760] melting point: 235-237° C. FAB-Ms: 520(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.58(2H, d, J=6.0 Hz), 8.23(1H, s), 7.96 and 7.86(2H, ABq, J=8.7 Hz), 7.68 and 7.17(4H, A′B′q, J=8.7 Hz), 7.44(2H, d, J=8.7 Hz), 7.39(1H, t, J=8.3 Hz), 6.90(1H, d, J=8.1 Hz), 6.84(1H, s), 6.75(1H, d, J=8.1 Hz), 5.22(2H, s), 4.40-4.22(1H, m), 2.40-2.19(2H, m), 2.00-1.80(4H, m)

EXAMPLE 241

Production of Methyl 2-{44-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1761] Step 1: Production of 2-bromo-5-methoxybenzaldehyde

[1762] 3-Methoxybenzaldehyde (15 g) was dissolved in acetic acid (75 ml), and a solution of bromine (5.7 ml) dissolved in acetic acid (15 ml) was added dropwise. The mixture was stirred overnight at room temperature and water (150 ml) was added to the reaction mixture. The precipitated crystals were collected by filtration, washed with water and dried under reduced pressure to give the title compound (21 g, yield 88%).

[1763] 1H-NMR (300 MHz, CDCl3): 10.31(1H, s), 7.52(1H, d, J=8.8 Hz), 7.41(1H, d, J=3.3 Hz), 7.03(1H, dd, J=8.8, 3.3 Hz), 3.48(3H, s)

[1764] Step 2: Production of 2-(4-chlorophenyl)-5-methoxybenzaldehyde

[1765] 2-Bromo-5-methoxybenzaldehyde (10 g) obtained in the previous step was treated in the same method as in Example 5 to give the title compound (11 g, yield 96%).

[1766] 1H-NMR (300 MHz, CDCl3): 9.92(1H, s), 7.50(1H, d, J=2.6 Hz), 7.48-7.14(6H, m), 3.90(3H, s)

[1767] Step 3: Production of 2-(4-chlorophenyl)-5-methoxybenzyl alcohol

[1768] 2-(4-Chlorophenyl)-5-methoxybenzaldehyde (10 g) obtained in the previous step was dissolved in tetrahydrofuran (30 ml). The solution was added dropwise to a suspension of sodium borohydride (620 mg) in isopropyl alcohol (50 ml) and the mixture was stirred for 1 hr. The solvent was evaporated under reduced pressure and water was added to the residue. The precipitated crystals were collected by filtration and dried under reduced pressure. The resulting crystals were recrystallized from a mixture of methanol and water to give the title compound (9.2 g, yield 91%).

[1769] 1H-NMR (300 MHz, CDCl3): 7.37(2H, d, J=8.6 Hz), 7.27(2H, d, J=8.6 Hz) 7.17(1H, d, J=8.6 Hz), 7.11(1H, d, J=2.6 Hz), 6.89(1H, dd, J=8.6, 2.6 Hz), 4.57(2H, s), 3.86(3H, s)

[1770] Step 4: Production of 2-(4-chlorophenyl)-5-methoxybenzyl chloride

[1771] 2-(4-Chlorophenyl)-5-methoxybenzyl alcohol (20 g) obtained in the previous step was dissolved in ethyl acetate (100 ml) and pyridine (0.5 ml), and thionyl chloride (11 ml) was added dropwise. The mixture was stirred for 1 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogencarbonate, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Isopropyl alcohol was added to the residue to allow crystallization. The resulting crystals were collected by filtration and dried under reduced pressure to give the title compound (16 g, yield 74%).

[1772] 1H-NMR (300 MHz, CDCl3): 7.43-7.29(4H, m), 7.17(1H, d, J=8.6 Hz), 7.05(1H, d, J=2.6 Hz), 6.96-6.89(1H, m), 4.46(2H, s), 3.86(3H, s)

[1773] Step 5: Production of Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1774] 2-(4-Chlorophenyl)-5-methoxybenzyl chloride (4.0 g) obtained in the previous step and methyl 1-cyclohexyl-2-(4-hydroxyphenyl)-benzimidazole-5-carboxylate (5.0 g) obtained in the same manner as in Example 3 were treated in the same manner as in Example 4 to give the title compound (6.0 g, yield 72%).

[1775] 1H-NMR (300 MHz, CDCl3): 8.48(1H, s), 8.00-7.93(1H, m), 7.68-7.62(1H, m), 7.54(2H, d, J=9.0 Hz), 7.41-7.16(6H, m), 7.04-6.93(3H, m), 4.97(2H, s), 4.36(1H, m), 3.94(3H, s), 3.87(3H, s), 2.39-2.21(2H, m), 2.02-1.88(4H, m), 1.85-1.45(4H, m)

EXAMPLE 242

Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride

[1776] Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (5.0 g) obtained in Example 241 was treated in the same manner as in Example 2 to give the title compound (5.1 g, yield 98%).

[1777] APCI-Ms: 568(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.30(1H, d, J=1.4 Hz), 8.24(1H, d, J=8.7 Hz), 8.03(1H, d, J=8.7 Hz), 7.72(2H, d, J=8.7 Hz), 7.51-7.39(4H, m), 7.34-7.18(4H, m), 7.11-7.03(1H, m), 5.08(2H, s), 4.35(1H, m), 3.83(3H,m), 2.40-2.18(2H, m), 2.10-1.96(2H, m), 1.93-1.78(2Hm), 1.72-1.18(4H, m)

EXAMPLE 243

Production of Ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1778] Step 1: Production of Methyl 3-hydroxypicolinate

[1779] 3-Hydroxypicolinic acid (1.0 g) was suspended in methanol (10 ml) and concentrated sulfuric acid (1.0 ml) was added. The mixture was refluxed under heating for 5 hr. The reaction mixture was ice-cooled, neutralized with saturated aqueous sodium hydrogencarbonate, and extracted with chloroform. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (711 mg, yield 64%).

[1780] 1H-NMR (300 MHz, CDCl3): 10.63(1H, s), 8.28(1H, dd, J=3.7, 1.8 Hz), 7.47-7.35(2H, m), 4.06(3H, s)

[1781] Step 2: Production of Methyl 3-(trifluoromethylsulfonyloxy)-pyridine-2-carboxylate

[1782] Methyl 3-hydroxypicolinate (710 mg) obtained in the previous step and triethylamine (0.77 ml) were dissolved in dichloromethane (7 ml), and trifluoromethanesulfonic anhydride (0.86 ml) was added under ice-cooling. The reaction mixture was allowed to warm to room temperature and the mixture was stirred for 2 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (1.2 g, yield 90%).

[1783] 1H-NMR (300 MHz, CDCl3): 8.80-8.73(1H, m), 7.75-7.70(1H, m), 7.63(1H, dd, J=8.2, 4.5 Hz), 4.05(3H, s)

[1784] Step 3: Production of Methyl 3-(4-chlorophenyl)pyridine-2-carboxylate

[1785] Methyl 3-(trifluoromethylsulfonyloxy)pyridine-2-carboxylate (1.2 g) obtained in the previous step was treated in the same manner as in Example 5 to give the title compound (728 mg, yield 69%).

[1786] 1H-NMR (300 MHz, CDCl3): 8.73-8.66(1H, m), 7.77-7.68(1H, m), 7.49(1H, dd, J=7.8, 4.5 Hz), 7.46-7.37(2H, m), 7.32-7.23(2H, m), 3.80(3H, s)

[1787] Step 4: Production of [3-(4-chlorophenyl)pyridin-2-yl]methanol

[1788] Methyl 3-(4-chlorophenyl)pyridine-2-carboxylate (720 mg) obtained in the previous step was dissolved in tetrahydrofuran (10 ml) and the solution was ice-cooled. Lithium aluminum hydride (160 mg) was added to the solution and the mixture was stirred for 1 hr. To the reaction mixture were added successively water (1.6 ml), 15% sodium hydroxide (1.6 ml) and water (4.8 ml) The insoluble materials were filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=1:1) to give the title compound (208 mg, yield 32%).

[1789] 1H-NMR (300 MHz, CDCl3): 8.60(1H, dd, J=4.8, 1.5 Hz), 7.60-7.55(1H, m), 7.40-7.48(2H, m), 7.29-7.36(1H, m), 7.27-7.20(3H, m), 4.63(2H, s)

[1790] Step 5: Production of Ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1791] [3-(4-Chlorophenyl)pyridin-2-yl]methanol (200 mg) obtained in the previous step was dissolved in chloroform (3 ml), and thionyl chloride (0.13 ml) and pyridine (catalytic amount) were added. The mixture was stirred for 1 hr at room temperature and concentrated under reduced pressure. The residue was dissolved in dimethylformamide (3 ml), and ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (232 mg) obtained in the same manner as in Example 3 and potassium carbonate (250 mg) were added. The mixture was stirred for 3 hr with heating at 80° C., The reaction mixture was then allowed to cool. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=1:2) to give the title compound (246 mg, yield 68%).

[1792] 1H-NMR (300 MHz, CDCl3): 8.71(1H, dd, J=4.7, 1.4 Hz), 8.49(1H, d, J=2.1 Hz), 7.96(1H, d, J=10.2 Hz), 7.71-7.62(2H, m), 7.53(2H, d, J=8.7 Hz), 7.45-7.34(5H, m), 7.04(2H, d, J=8.7 Hz), 5.14(2H, s), 4.48-4.29(3H, m), 2.38-2.19(2H, m), 2.02-1.22(1H, m)

EXAMPLE 244

Production of Methyl 2-[4-(2-bromo-5-tert-butoxycarbonyl-benzyloxy),phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1793] Step 1: Production of tert-butyl 4-bromo-3-methylbenzoate

[1794] 4-Bromo-3-methylbenzoic acid (25 g), was suspended in dichloromethane (200 ml), and oxalyl chloride (12 ml) and dimethylformamide (catalytic amount) were added. The mixture was stirred for 2 hr at room temperature and the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (200 ml) and the solution was ice-cooled. To the solution was added dropwise a solution of potassium tert-butoxide dissolved in tetrahydrofuran (150 ml) and the mixture was stirred for 30 min. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (27 g, yield 85%).

[1795] 1H-NMR (300 MHz, CDCl3): 7.83(1H, d, J=2.22 Hz), 7.67-7.53(2H, m), 2.43(3H, s), 1.58(9H, s)

[1796] Step 2: Production of Methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate tert-Butyl 4-bromo-3-methylbenzoate (7.0 g) obtained in the previous step and methyl 1-cyclohexyl-2-(4-hydroxyphenyl)-benzimidazole-5-carboxylate (6.3 g) obtained in the same manner as in Example 3 were treated in the same manner as in Example 4 to give the title compound (8.8 g, yield 77%).

[1797] 1H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.5 Hz), 8.21(1H, d, J=2.1 Hz), 7.97(1H, d, J=10.2 Hz), 7.82(1H, d, J=10.2 Hz), 7.71-7.58(4H, m), 7.16(2H, d, J=8.7 Hz), 5.23(2H, s), 4.38(1H, m), 3.95(3H, s), 2.40-2.23(2H, m), 2.04-1.90(4H, m), 1.84-1.73(1H, m), 1.59(9H, s), 1.44-1.27(3H, m)

EXAMPLE 245

Production of Methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1798] Methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-3-1-cyclohexylbenzimidazole-5-carboxylate (4.5 g) obtained in Example 244 was treated in the same manner as in Example 5 to give the title compound (3.6 g, yield 76%).

[1799] 1H-NMR (300 MHz, CDCl3): 8.48(1H, s), 8.27(1H, d, J=1.8 Hz), 8.04(1H, dd, J=7.9, 1.5 Hz), 7.96(1H, dd, J=7.0, 1.5 Hz), 7.65(1H, d, J=8.6 Hz), 7.55(2H, d, J=8.6 Hz), 7.43-7.32(5H, m), 7.01(2H, d, J=8.6 Hz), 4.99(2H, s), 4.43-4.29(1H, m), 3.95(3H, s), 2.41-2.21(2H, m), 2.02-1.89(4H, m), 1.82-1.73(1H, m), 1.62(9H, s), 1.46-1.28(3H, m)

EXAMPLE 246

Production of Methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride

[1800] Methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (3.5 g) obtained in Example 245 was dissolved in dichloromethane (35 ml), and trifluoroacetic acid (35 ml) was added. The mixture was stirred for 1 hr at room temperature and the reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and 4N hydrochloric acid-ethyl acetate was added. The precipitated crystals were collected by filtration and dried under reduced pressure to give the title compound (3.3 g, yield 97%).

[1801] 1H-NMR (300 MHz, DMSO-d6): 8.33(1H, d, J=1.5 Hz), 8.29(1H, s), 8.24(1H, d, J=1.8 Hz), 8.09-8.00(2H, m), 7.74(2H, d, J=8.6 Hz), 7.61-7.44(5H, m), 7.24(2H, d, J=8.6 Hz), 5.19(2H, s), 4.36(1H, m), 3.93(3H, s), 2.37-1.21(10H, m)

EXAMPLE 247

Production of Methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoyl-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1802] Methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (400 mg) obtained in Example 246 was suspended in dichloromethane (5 ml), and oxalyl chloride (0.08 ml) and dimethylformamide (catalytic amount) were added. The mixture was stirred for 2 hr at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in dichloromethane (5 ml). The resulting solution was added dropwise to a mixed solution of 40% aqueous methylamine solution (5 ml) and tetrahydrofuran (5 ml) under ice-cooling. The reaction mixture was stirred for 1 hr and concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogencarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was crystallized from ethyl acetate and diisopropyl ether. The crystals were collected by filtration and dried under reduced pressure to give the title compound (335 mg, yield 86%).

[1803] 1H-NMR (300 MHz, CDCl3): 8.47(1H, s), 8.06(1H, d, J=1.8 Hz), 7.96(1H, dd, J=8.6, 1.5 Hz), 7.82(1H, dd, J=8.2, 2.2 Hz), 7.64(1H, d, J=8.6 Hz), 7.54(2H, d, J=9.0 Hz), 7.44-7.31(5H, m), 6.99(2H, d, J=9.0 Hz), 6.35-6.26(1H, m), 5.00(2H, s), 4.35(1H, m), 3.95(3H, s), 3.05(3H, d, J=4.8 Hz), 2.40-1.24(10H, m)

EXAMPLE 248

Production of 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride

[1804] Methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (150 mg) obtained in Example 247 and tetrahydrofuran (2 ml) were treated in the same manner as in Example 2 to give the title compound (141 mg, yield 90%).

[1805] APCI-Ms: 594(MH+) 1H-NMR (300 MHz, DMSO-d6) 8.65-8.58(1H, m), 8.27(1H, d, J=1.5 Hz) 8.21(1H, d, J=8.2 Hz), 8.15(1H, d, J=1.5 Hz), 8.05-7.90(2H, m), 7.70(2H, d, J=8.6 Hz), 7.56-7.43(5H, m), 7.21(2H, d, J=8.6 Hz), 5.14(2H, s), 4.34(1H, m), 2.81(3H, d, J=4.5 Hz), 2.39-1.19(10H, m)

EXAMPLE 336

Production of Methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1806] Commercially available 2-bromo-5-nitrotoluene was dissolved in carbon tetrachloride (30 ml), and N-bromosuccinimide (2.9 g) and N,N′-azobisisobutyronitrile (228 mg) were added, which was followed by refluxing under heating overnight. The reaction mixture was allowed to cool, water was added and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dimethylformamide (30 ml) and methyl 2-(2-fluoro-4-hydroxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylate (3.8 g) obtained in the same manner as in Example 3 and potassium carbonate (3.8 g) were added, which was followed by stirring at 80° C. for 1 hr. The reaction mixture was allowed to cool, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=1:1) to give the title compound (3.7 g, yield 61%).

[1807] 1H-NMR (300 MHz, CDCl3): 8.55-8.45(2H, m), 8.15-8.05(1H, m), 7.99(1H, dd, J=8.6 Hz, 1.5 Hz), 7.70-7.55(2H, m), 7.05-6.85(2H, m), 5.24(2H,s), 4.06(1H, m), 3.95(3H, s), 2.35-2.15(2H, m), 2.05-1.85(4H, m), 1.80-1.70(1H, m), 1.45-1.20(3H, m)

EXAMPLE 337

Production of Methyl 2-[4-2-(4-chlorophenyl)-5-nitrobenzyloxy-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1808] Methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (2.0 g) obtained in Example 336, 4-chlorophenylboronic acid (590 mg) and tetrakis (triphenylphosphine) palladium (396 mg) were suspended in dimethoxyethane (40 ml), and saturated aqueous sodium hydrogencarbonate solution (20 ml) was added, which was followed by refluxing under heating for 1 hr. The reaction mixture was allowed to cool, water was added and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (n-hexane:ethyl acatate=2:1) to give the title compound (1.9 g, yield 90%).

[1809] 1H-NMR (300 MHz, CDCl3): 8.55(1H, d, J=2.3 Hz), 8.49(1H, d, J=1.4 Hz), 8.29(1H, dd, J=8.4 Hz, 2.3 Hz), 7.98(1H, dd, J=8.6 Hz, 1.5 Hz), 7.60-7.30(6H, m), 6.85-6.70(2H, m), 5.03(2H, s), 4.02(1H, m), 3.95(3H, s), 2.35-2.10(2H, m), 2.05-1.70(5H, m), 1.40-1.20(3H, m)

EXAMPLE 338

Production of Methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1810] Methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (1.9 g) obtained in Example 337 was suspended in ethanol (40 ml), and tin(II) chloride dihydrate (3.5 g) was added, which was followed by refluxing under heating for 30 min. The reaction mixture was concentrated under reduced pressure, 4N sodium hydroxide was added and the mixture was extracted with chloroform. The organic layer was washed with 2N sodium hydroxide and water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Diisopropyl ether was added to the residue, and the precipitated crystals were collected by filtration to give the title compound (1.5 g, yield 82%).

[1811] 1H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.2 Hz), 7.98(1H, dd, J=9.0, 1.5 Hz), 7.66(1H, d, J=8.7 Hz), 7.49(1H, t, J=8.4 Hz), 7.40-7.20(3H, m), 7.13(1H, d, J=8.1 Hz), 6.92(1H, d, J=2.7 Hz), 6.85-6.65(4H, m) 4.92(2H, s), 4.03(1H, m), 3.95(3H, s), 3.82(2H, brs), 2.30-2.10(2H, m), 2.05-1.80(4H, m), 1.80-1.70(1H, m), 1.40-1.10(3H, m)

EXAMPLE 339

Production of Methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1812] Methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (500 mg) obtained in Example 338 and triethylamine (0.14 ml) were dissolved in chloroform (5 ml), and commercially available chlorobutyryl chloride (0.1 ml) was added under ice-cooling, which was followed by stirring at room temperature for 3 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dimethylformamide (6 ml) and potassium carbonate (244 mg) was added, which was followed by stirring at 80° C. for 1 hr. The reaction mixture was allowed to cool, water was added and the precipitated crystals were collected by filtration to give the title compound (502 mg, yield 89%).

[1813] 1H-NMR (300 MHz, CDCl3): 4.89(1H, d, J=1.5 Hz), 7.98(1H, dd, J=8.6 Hz, 1.6 Hz), 7.72(1H, d, J=2.2 Hz), 7.75-7.65(2H, m), 7.49(1H, t, J=8.3 Hz), 7.45-7.20(5H, m), 6.85-7.65(2H, m), 4.99(2H, s), 4.10-3.85(6H, m), 2.66(2H, t, J=7.8 Hz), 2.30-2.15(4H, m), 2.00-1.85(4H, m), 1.80-1.70(1H, m), 1.45-1.20(3H, m)

EXAMPLE 340

Production of 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride

[1814] Methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (200 mg) obtained in Example 339 was treated in the same manner as in Example 2 to give the title compound (182 mg, yield 87%).

[1815] Ms:638(M+1) 1H-NMR (300 MHz, CDCl3) 8.28(1H, d, J=1.3 Hz), 8.10(1H, d, J=8,7 Hz), 8.05-7.90(2H, m), 7.77(1H, dd, J=8.4 Hz, 2.2 Hz), 7.61(1H, t, J=8.5 Hz), 7.55-7.35(5H, m), 7.00-7.20(2H, m), 5.09(2H, s), 4.06(1H, m), 3.90(2H, t, J=6.9 Hz), 2.60-2.45(2H, m), 2.30-2.00(4H, m), 1.95-1.75(4H, m), 1.70-1.55(1H, m), 1.45-1.15(3H, m)

[1816] In the same manner as in Examples 1-30, 241-248 and 336-340 and optionally using other conventional methods, where necessary, the compounds of Examples 31-240, 249-335, 341-446, 701-703 and 1001-1559 were obtained. The chemical structures and properties are shown in Table 1 to 177, 185 to 212, 219 to 221 and 225 to 260.

EXAMPLE 501

Production of Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate

[1817] Step 1: Production of Methyl 3-bromo-4-cyclohexylaminobenzoate

[1818] 3-Bromo-4-fluorobenzoic acid (2.0 g) was dissolved in methanol (20 ml) and concentrated sulfuric acid (2 ml) was added. The mixture was refluxed for 3 hr. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate (50 ml). The organic layer was washed with water (30 ml) and saturated brine (30 ml), and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The residue was dissolved in dimethyl sulfoxide (20 ml) and cyclohexylamine (10.3 ml) was added. The mixture was stirred overnight at 120° C., The reaction mixture was poured into 10% aqueous citric acid solution (100 ml) and extracted with ethyl acetate (100 ml). The organic layer was washed with water (50 ml) and saturated brine (50 ml), and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=10:1) to give the title compound (2.6 g, yield 92%).

[1819] 1H-NMR (300 MHz, CDCl3): 8.10(1H, d, J=1.9 Hz), 7.83(1H, dd, J=1.9 Hz, 8.6 Hz), 6.59(1H, d, J=8.7 Hz), 4.73(1H, brd, J=7.3 Hz), 3.85(3H, s), 3.38(1H, m), 2.10-2.00(2H, m), 1.90-1.20(8H, m)

[1820] Step 2: Production of 4′-chloro-2-(4-iodophenoxymethyl)-4-methoxybiphenyl

[1821] 4-Iodophenol (5.0 g) was dissolved in acetone (50 ml), and potassium carbonate (4.7 g) and 4′-chloro-2-chloromethyl-4-methoxybiphenyl (6.0 g) obtained in Example 241, Step 4 were added. The mixture was refluxed for 10 hr. The reaction mixture was concentrated and 4N aqueous sodium hydroxide solution (50 ml) was added. The precipitated crystals were collected by filtration, washed with water, and dried under reduced pressure to give the title compound (10.0 g, yield 98%).

[1822] 1H-NMR (300 MHz, CDCl3): 7.52(2H, d, J=8.9 Hz), 7.35(2H, d, J=8.5 Hz), 7.27-7.20(3H, m), 7.12(1H, s), 6.95(1H, d, J=8.5 Hz), 6.62(2H, d, J=8.9 Hz), 4.84(2H, s), 3.85(3H, s)

[1823] Step 3: Production of [4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]trimethylsilane

[1824] 4′-Chloro-2-(4-iodophenoxymethyl)-4-methoxybiphenyl (7.0 g) obtained in the previous step was dissolved in acetonitrile (50 ml), and trimethylsilylacetylene (2.3 g), tetrakis-(triphenylphosphine)palladium complex (1.8 g), copper(I) iodide (0.6 g) and triethylamine (50 ml) were added. The mixture was stirred overnight at room temperature and concentrated. Water (30 ml) was added and the mixture was extracted with ethyl acetate (50 ml). The organic layer was washed with water (30 ml) and saturated brine (30 ml) and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel flash chromatography. (developing solvent, n-hexane:ethyl acetate=10:1) to give the title compound (5.1 g, yield 79%).

[1825] 1H-NMR (300 MHz, CDCl3): 7.37(2H, d, J=8.9 Hz), 7.34(2H, d, J=8.2 Hz), 7.28-7.21(3H, m), 7.13(1H, s), 6.94(1H, d, J=8.2 Hz), 6.75(2H, d, J=8.9 Hz), 4.87(2H, s), 3.85(3H, s); 0.23(9H, s)

[1826] Step 4: Production of Methyl 3-[4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]-4-cyclohexylaminobenzoate

[1827] [4-(4′-Chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]-trimethylsilane (5.1 g) obtained in the previous step was dissolved in methanol (50 ml) and chloroform (50 ml), and potassium carbonate (2.5 g) was added. The mixture was stirred for 3 hr at room temperature and concentrated. Water (30 ml) was added and the mixture was extracted with ethyl acetate (50 ml). The organic layer was washed with water (30 ml) and saturated brine (30 ml) and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure to give white crystals (3.8 g). The white crystals (2.3 g) were dissolved in acetonitrile (10 ml), and methyl 3-bromo-4-cyclohexylamino-benzoate (1.0 g) obtained in Step 1, tetrakis(triphenyl-phosphine)palladium complex (0.4 g), copper(I) iodide (0.1 g) and triethylamine (10 ml) were added. The mixture was stirred overnight at 100° C. and concentrated under reduced pressure. Water (30 ml) was added and the mixture was extracted with ethyl acetate (50 ml). The organic layer was washed with water (30 ml) and saturated brine (30 ml), and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=8:1) to give the title compound (0.9 g, yield 49%).

[1828] 1H-NMR (300 MHz, CDCl3): 8.03(1H, s), 7.84(1H, d, J=8.7 Hz), 7.42-7.22-(7H, m), 7.15(1H, s), 6.95(1H, d, J=8.2 Hz), 6.85(2H, d, J=8.8 Hz), 6.59(1H, d, J=8.8 Hz), 5.07(1H, brs), 4.91(2H, s), 3.86(3H, s), 3.85(3H, s), 3,42(1H, m), 2.15-2.00(2H, m), 1.80-1.20(8H, m)

[1829] Step 5: Production of Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate

[1830] Methyl 3-[4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenyl-ethynyl]-4-cyclohexylaminobenzoate (0.5 g) obtained in the previous step was dissolved in N,N-dimethylformamide (5 ml), and copper(I) iodide (0.17 g) was added. The mixture was refluxed for 3 hr at 180° C., The insoluble materials were removed by filtration. Water (10 ml) was added and the mixture was extracted with ethyl acetate (30 ml). The organic layer was washed with water (10 ml) and saturated brine (10 ml), and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=8:1) to give the title compound (0.27 g, yield 55%).

[1831] 1H-NMR (300 MHz, CDCl3): 8.34(1H, s), 7.85(1H, d, J=8.8 Hz), 7.62(1H, d, J=8.8 Hz), 7.40-7.18(8H, m), 7.00-6.94(3H, m), 6.48(1H, s), 4.95(2H, m), 4.18(1H, m), 3.93(3H, s), 3.88(3H, s), 2.45-2.25(2H, m), 1.95-1.20(8H, m)

EXAMPLE 502

Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic acid

[1832] Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate (0.27 g) obtained in Example 501 was treated in the same manner as in Example 2 to give the title compound (0.19 g, yield 71%).

[1833] APCI-Ms: 566(MH+)

[1834] 1H-NMR (300 MHz, DMSO-d6): 12.43(1H, brs), 8.20(1H, s), 7.79(1H, d, J=9.3 Hz), 7.72(1H, d, J=9.0 Hz), 7.50-7.20(8H, m), 7.07-7.03(3H, m), 6.53(1H, s), 5.01(2H, s), 4.13(1H, m), 3.83(3H, m), 2.35-2.25(2H, m), 1.85-1.10(8H, m)

[1835] In the same manner as in Examples 501 and 502, and optionally using other conventional methods where necessary, the compound of Example 503 was obtained. The chemical structure and properties are shown in Table 207.

EXAMPLE 601

Production of Ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo-[1,2-a]pyridine-7-carboxylate

[1836] Step 1: Production of 4-benzyloxy-N-methoxy-N-methylbenzamide 4-Benzyloxybenzoic acid (5.0 g) and N,O-dimethyl-hydroxylamine hydrochloride (2.5 g) were suspended in dimethylformamide (50 ml), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.0 g), 1-hydroxybenzotriazole (3.5 g) and triethylamine (3.6 ml) were added. The mixture was stirred overnight at room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water, saturated aqueous sodium hydrogencarbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (5.6 g, yield 94%).

[1837] 1H-NMR (300 MHz, CDCl3): 7.22, 2H, d, J=8.8 Hz), 7.28-7.46(5H, m), 6.97(2H, d, J=8.8 Hz), 5.10(2H, s), 3.56(3H, s), 3.35(3H, s)

[1838] Step 2: Production of 1-(4-benzyloxyphenyl)-2-cyclohexylethanone

[1839] Magnesium (470 mg) was suspended in tetrahydrofuran (2 ml) and cyclohexylmethyl bromide (3.4 g) was added dropwise at room temperature. After the addition, the reaction mixture was stirred for 30 min at 60° C., The reaction mixture was allowed to cool and diluted with tetrahydrofuran (5 ml). Separately, 4-benzyloxy-N-methoxy-N-methylbenzamide (3.4 g) obtained in the previous step was dissolved in tetrahydrofuran (10 ml) and the solution was added dropwise to the reaction mixture at-room temperature. The mixture was stirred for 2 hr and saturated aqueous ammonium chloride solution was added to the reaction mixture. The mixture was extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate 9:1) to give the title compound (3.8 g, yield 66%).

[1840] 1H-NMR (300 MHz, CDCl3): 7.93(2H, d, J=8.8 Hz), 7.28-7.46(5H, m), 7.00(2H, d, J=8.8 Hz), 5.13(2H, s), 2.76(2H, d, J=6.8 Hz), 1.95(1H, m), 0.78-1.82(10 H, m)

[1841] Step 3: Production of 1-(4-benzyloxyphenyl)-2-bromo-2-cyclohexylethanone

[1842] 1-(4-Benzyloxyphenyl)-2-cyclohexylethanone (1.0 g) obtained in the previous step was dissolved in 1,4-dioxane (10 ml) and bromine (0.17 ml) was added. The mixture was stirred for 10 min at room temperature. Saturated aqueous sodium hydrogencarbonate was added to the reaction mixture and the mixture was extracted with diethyl ether. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=9:1) to give the title compound (696 mg, yield 55%),

[1843] 1H-NMR (300 MHz, CDCl3): 7.98(2H, d, J=8.9 Hz), 7.28-7.48(5H, m), 7.02(2H, d, J=8.9 Hz), 5.14(2H, s), 4.89(1H, d, J=9.3 Hz), 0.86-3.30(1H, m)

[1844] Step 4: Production of Ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate

[1845] Ethyl 2-aminopyridine-4-carboxylate (214 mg) prepared. according to JP-A-8-48651, 1-(4-benzyloxyphenyl)-2-bromo-2-cyclohexylethanone (500 mg) obtained in the previous step and potassium carbonate (356 mg) were stirred for 5 hr with heating at 140° C. The reaction mixture was allowed to cool and chloroform was added. The insoluble materials were filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=1:1) to give the title compound (95 mg, yield 16%).

[1846] APCI-MS: 455(MH+) 1H-NMR (300 MHz, CDCl3): 8.33(1H, s), 8.21(1H, d, J=7.5 Hz), 7.55(2H, d, J=8.7 Hz), 7.25-7.50(6H, m), 5.13(2H, s), 4.41(2H, q, J=7.1 Hz), 3.25(1H, m), 1.41(3H, t, J=7.1 Hz), 1.15-2.00(10H, m)

EXAMPLE 602

Production of 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid

[1847] Ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate (95 mg) obtained in the previous step was treated in the same manner as in Example 2 to give the title compound (33 mg, 37%).

[1848] APCI-MS: 427(MH+)

[1849] 1H-NMR (300 MHz, DMSO-d6): 8.67(1H, d, J=7.3 Hz), 8.08(1H, s), 7.25-7.58(8H, m), 7.13(2H, d, J=8.7 Hz), 5.17(2H, s), 3.23(1H, m), 1.25-2.10(10 H, m)

[1850] The compounds shown in Tables 213 to 218 can be further obtained in the same manner as in Examples 1 to 701 or by other conventional method employed as necessary.

[1851] The evaluation of the HCV polymerase inhibitory activity of the compound of the present invention is explained in the following. This polymerase is an enzyme coded for by the non-structural protein region called NS5B on the RNA gene of HCV (EMBO J., 15:12-22, 1996).

EXPERIMENTAL EXAMPLE I

i) Preparation of Enzyme (HCV Polymerase)

[1852] Using, as a template, a cDNA clone corresponding to the full length RNA gene of HCV BK strain obtained from the blood of a patient with hepatitis C, a region encoding NS5B (591 amino acids; J Virol 1991 March, 65(3), 1105-13) was amplified by PCR. The objective gene was prepared-by adding a 6 His tag {base pair encoding 6 continuous histidine (His)} to the 5′ end thereof and transformed to Escherichia coli. The Escherichia coli capable of producing the objective protein was cultured. The obtained cells were suspended in a buffer solution containing a surfactant and crushed in a microfluidizer. The supernatant was obtained by centrifugation and applied to various column chromatographys {poly[U]-Sepharose, Sephacryl S-200, mono-S (Pharmacia)}, inclusive of metal chelate chromatography, to give a standard enzyme product.

ii) Synthesis of Substrate RNA

[1853] Using a synthetic primer designed based on the sequence of HCV genomic 3′ untranslated region, a DNA fragment (148 bp) containing polyU and 3′X sequence was entirely synthesized and cloned into plasmid pBluescript SK II(+) (Stratagene). The cDNA encoding full length NS5B, which was prepared in i) above, was digested with restriction enzyme KpnI to give a cDNA fragment containing the nucleotide sequence of from the restriction enzyme cleavage site to the termination codon. This cDNA fragment was inserted into the upstream of 3′ untranslated region of the DNA in pBluescript SK II(+) and ligated. The about 450 bp inserted DNA sequence was used as a template in the preparation of substrate RNA. This plasmid was cleaved immediately after the 3′X sequence, linearized and purified by phenol-chloroform treatment and ethanol precipitation to give DNA.

[1854] RNA was synthesized (37° C., 3 hr) by run-off method using this purified DNA as a template, a promoter of pBluescript SK II(+), MEGAscript RNA synthesis kit (Ambion) and T7 RNA polymerase. DNaseI was added and the mixture was incubated for 1 hr. The template DNA was removed by decomposition to give a crude RNA product. This product was treated with phenol-chloroform and purified by ethanol precipitation to give the objective substrate RNA.

[1855] This RNA was applied to formaldehyde denaturation agarose gel electrophoresis to confirm the quality thereof and preserved at −80° C.,

iii) Assay of Enzyme (HCV Polymerase) Inhibitory Activity

[1856] A test substance (compound of the present invention) and a reaction mixture (30 &mgr;l) having the following composition were reacted at 25° C. for 90 min.

[1857] 10% Trichloroacetic acid at 4° C. and 1% sodium pyrophosphate solution (150 &mgr;l) were added to this reaction mixture to stop the reaction. The reaction mixture was left standing in ice for 15 min to insolubilize RNA. This RNA was trapped on a glass filter (Whatman GF/C and the like) upon filtration by suction. This filter was washed with a solution containing 1% trichloroacetic acid and 0.1% sodium pyrophosphate, washed with 90% ethanol and dried. A liquid scintillation cocktail (Packard) was added and the radioactivity of RNA synthesized by the enzyme reaction was measured on a liquid scintillation counter.

[1858] The HCV polymerase inhibitory activity (IC50) of the compound of the present invention was calculated from the values of radioactivity of the enzyme reaction with and without the test substance.

[1859] The results are shown in Tables 178-184 and 222-224.

[1860] Reaction mixture HCV polymerase (5 &mgr;g/ml) obtained in i), substrate RNA (10 &mgr;g/ml) obtained in ii), ATP (50 &mgr;M), GTP (50 &mgr;M), CTP (50 &mgr;M), UTP (2 &mgr;M), [5,6-3H]UTP (46 Ci/mmol (Amersham), 1.5 &mgr;Ci) 20 mM Tris-HCl (pH 7.5), EDTA (1 MM), MgCl2 (5 mM), NaCl (50 mM), DTT (1 mM), BSA (0.01%) 1 TABLE 1 Example No. 31 1H NMR(&dgr;) ppm 95 300 MHz, CDCl3 7.81 (2H, d, J=6.6 Hz), 7.60 (2H, d, J=8.8 Hz), 7.51-7.21 (8H, m), 7.11 (2H, d, J=8.8 Hz), 5.15 (2H, s), 4.93 (1H, quint, J=8.8 Hz), 2.36-2.32 (2H, m), 2.09-2.04 (3H, m), 1.75-1.68 (3H, m). Purity >90% (NMR) MS 369 (M + 1) Example No. 32 1H NMR(&dgr;) ppm 96 300 MHz, CDCl3 8.51(1H, d, J=1.5 Hz), 7.98 (1H, d, J=8.4 Hz), 7.61 (2H, d, J=8.7 Hz), 7.56-7.10 (6H, m), 7.12 (2H, d, J=8.7 Hz), 5.15 (2H, s), 4.94 (1H, quint, J=9.3 Hz), 4.41 (2H, q, J=7.5 Hz), 2.40-1.50 (8H, m), 1.41 (3H, t, J=7.5 Hz) Purity >90% (NMR) MS 441 (M + 1) Example No. 33 1H NMR(&dgr;) ppm 97 300 MHz, CDCl3 7.84(1H, s), 7.61(2H, d, J=9.0 Hz), 7.58-7.30(7H, m), 7.12(2H, d, J=9.0 Hz), 5.15(2H, s), 4.94(1H, quint, J=8.7 Hz), 3.10 (6H, brs), 2.40-1.50 (8H, m) Purity >90% (NMR) MS 440 (M + 1)

[1861] 2 TABLE 2 Example No. 34 1H NMR (&dgr;) ppm 98 300 MHz, CDCl3 8.20 (1H, s), 7.50-7.31 (9H, m), 7.12 (2H, d, J=8.7 Hz), 5.15 (2H, s), 4.94(1H, quint, J=8.7 Hz), 3.61 (3H, s), 3.40 (3H, s), 2.41-1.42 (8H, m) Purity >90% (NMR) MS 456 (M + 1) Example No. 35 1H NMR (&dgr;) ppm 99 300 MHz, CDCl3 7.91(1H. s), 7.59 (2H, d, J=8.7 Hz), 7.49-7.30 (7H, m), 7.11 (2H, d, J=8.8 Hz), 5.15 (2H, s), 4.19 (1H, quint, J=8.8 Hz), 2.41-2.22 (2H, m), 2.13-1.49 (14H, m) Purity >90% (NMR) MS 427 (M + 1) Example No. 36 1H NMR (&dgr;) ppm 100 300 MHz, CDCl3 8.40 (1H, d, J=1.4 Hz), 7.95 (1H, dd, J=8.6, 1.4 Hz), 7.61 (2H, d, J=8.7 Hz), 7.57-7.30 (6H, m), 7.13 (2H, d, J=8.7 Hz), 5.16 (2H, s), 4.95 (1H, quint, J=8.8 Hz), 2.64(3H, s), 2.40-1.54(8H, m) Purity >90% (NMR) MS 411 (M + 1)

[1862] 3 TABLE 3 Example No. 37 1H NMR (&dgr;) ppm 101 300 MHz, DMSO-d6 10.47(1H, brs,), 9.15(1H, brs), 8.40 (1H, s), 8.07 (1H, d, J=9.0 Hz), 7.93 (1H, d, J=8.7 Hz), 7.77 (2H, d, J=8.7 Hz), 7.55-7.29(7H, m), 5.26 (2H, s), 4.93 (1H, quint, J=9.0 Hz), 3.77-3.63 (2H, m), 3.39-3.23 (2H, m), 2.84 (6H, d, J=4.8 Hz), 2.32-1.60 (8H, m) Purity >90% (NMR) MS 483 (M + 1) Example No. 38 1H NMR (&dgr;) ppm 102 300 MHz, CDCl3 8.69(1H, s), 8.19(1H, d, J=9.0 Hz), 7.62 (2H, d, J=8.7 Hz), 7.54(1H, d, J=9.0 Hz), 7.48-7.36 (5H, m), 7.15 (2H, d, J=8.7 Hz), 5.17 (2H, s), 4.98 (1H, quint, J=9.0 Hz), 2.27-2.07 (6H, m), 1.82-1.78 (2H, m). Purity >90% (NMR) MS 414 (M + 1) Example No. 39 1H NMR (&dgr;) ppm 103 300 MHz, DMSO-d6 7.84 (1H, d, J=9.0 Hz), 7.79 (2H, d, J=8.7 Hz), 7.52-7.33 (8H, m), 7.26(1H, d, J=9.0 Hz), 5.27 (2H, s), 4.92 (1H, quint, J=9.3 Hz), 2.19-1.70 (8H, m). Purity >90% (NMR) MS 384 (M + 1)

[1863] 4 TABLE 4 Example No. 40 1H NMR(&dgr;) ppm 104 300 MHz, CDCl3 7.72 (1H, s), 7.60-7.35 (10H, m), 7.10 (2H, d, J=8.7 Hz), 5.14 (2H, s), 4.90 (1H, quint, J=8.8 Hz), 2.29-2.19 (2H, m), 2.19 (3H, s), 2.19-1.74 (6H, m). Purity >90% (NMR) MS 426 (M + 1) Example No. 41 1H NMR(&dgr;) ppm 105 300 MHz, CDCl3 7.66 (1H, s), 7.61 (2H, d, J=8.8 Hz), 7.50-7.28 (7H, m), 7.12 (2H, d, J=8.8 Hz), 6.86 (1H, brs), 5.15 (2H, s), 4.94 (1H, quint, J=8.8 Hz), 2.97 (3H, s), 2.29-1.76 (8H, m). Purity >90% (NMR) MS 462 (M + 1) Example No. 42 1H NMR(&dgr;) ppm 106 300 MHz, DMSO 8.11 (1H, s), 7.81 (1H, d, J=8.4 Hz), 7.72 (1H, d, J=8.4 Hz), 7.65(2H, d, J=8.4 Hz), 7.51 (2H, m), 7.43 (2H, m), 7.37 (1H, m), 7.29 (2H, s), 7.23 (2H, d, J=8.4 Hz), 5.22 (2H, s), 4.89 (1H, quintet, J=9.2 Hz), 2.2-2.0 (6H, m), 1.7 (2H, m). Purity >90% (NMR) MS 448 (M+)

[1864] 5 TABLE 5 Example No. 43 1H NMR(&dgr;) ppm 107 300 MHz, DMSO-d6 8.33 (1H, s), 8.08 (1H, d, J=9.0 Hz), 7.99 (1H, d, J=9.0 Hz), 7.47-7.41 (4H, m), 7.33 (2H, d, J=8.4 Hz), 5.22 (2H, s), 4.96 (1H, quint, J=9.0 Hz), 2.25-1.60 (8H, m), 1.30 (9H, s). Purity >90% (NMR) MS 469 (M + 1) Example No. 44 1H NMR(&dgr;) ppm 108 300 MHz, DMSO-d6 12.9 (2H, brs), 8.25 (1H, s), 8.00(2H, d, J=7.8 Hz), 7.90 (1H, d, J=8.4 Hz), 7.74(1H, d, J=8.7 Hz), 7.67 (2H, d, J=9.0 Hz), 7.62 (2H, d, J=8.1 Hz), 7.24(2H, d, J=8.4 Hz), 5.32 (2H, s), 4.88 (1H, quint, J=9.0 Hz, 2.25-1.60 (8H, m). Purity >90% (NMR) MS 457 (M + 1) Example No. 45 1H NMR(&dgr;) ppm 109 300 MHz, DMSO-d6 13.4 (1H, brs), 8.32 (1H, s), 8.06 (1H, d, J=8.7 Hz), 7.97 (1H, d, J=8.7 Hz), 7.79 (2H, d, J=8.8 Hz), 7.56-7.48 (4H, m), 7.33(2H, d, J=8.8 Hz), 5.27 (2H, s), 4.95 (1H, quint, J=8.9 Hz), 2.30-1.60 (8H, m). Purity >90% (NMR) MS 447 (M + 1)

[1865] 6 TABLE 6 Example No. 46 1H NMR(&dgr;) ppm 110 300 MHz, DMSO-d6 8.33(1H, s), 8.07 (1H, d, J=8.7 Hz), 7.98 (1H, d, J=8.7 Hz), 7.80 (2H, d, J=8.4 Hz), 7.34 (2H, d, 8.4 Hz), 7.19 (1H, d, J=3.6 Hz), 7.09(1H, d, J=3.6 Hz), 5.41 (2H, s), 4.95 (1H, quint, J=8.7 Hz), 2.30-1.60 (8H, m). Purity >90% (NMR) MS 453 (M + 1) Example No. 47 1H NMR(&dgr;) ppm 111 300 MHz, DMSO-d6 8.33 (1H, s), 8.07 (1H, d, J=8.4 Hz), 7.98 (1H, d, J=9.0 Hz), 7.82-7.72 (6H, m), 7.35 (2H, d, J=9.0 Hz), 5.40 (2H, s), 4.95 (1H, quint, J=8.7 Hz), 2.35-1.60 (8H, m). Purity >90% (NMR) MS 481 (M + 1) Example No. 48 1H NMR(&dgr;) ppm 112 300 MHz, DMSO-d6 8.23 (1H, s), 7.88 (1H, d, J=8.4 Hz), 7.70 (1H, d, J=8.4 Hz), 7.64(2H, d, J=8.4 Hz), 7.43 (2H, d, J=8.4 Hz), 7.20 (2H, d, J=8.4 Hz), 6.98 (2H, d, J=8.4 Hz), 5.13 (2H, s), 4.88 (1H, quint, J=8.7 Hz), 3.77 (3H, s), 2.35-1.60 (8H, m). Purity >90% (NMR) MS 443 (M + 1)

[1866] 7 TABLE 7 Example No. 49 1H NMR (&dgr;) ppm 113 300 MHz, DMSO-d6 8.93 (2H, d, J=6.6 Hz), 8.35 (1H, s), 8.06-8.04 (3H, m), 7.97 (1H, d, J=8.7 Hz), 7.83 (2H, d, J=8.7 Hz), 7.38 (2H, d, J=8.7 Hz), 5.61 (2H, s), 4.94 (1H, quint, J=8.7 Hz), 2.40-1.60 (8H, m). Purity >90% (NMR) MS 414 (M + 1) Example No. 50 1H NMR (&dgr;) ppm 114 300 MHz, DMSO-d6 8.33 (1H, s), 8.08 (1H, d, J=8.7 Hz), 7.99 (1H, d, J=9.0 Hz), 7.78 (2H, d, J=8.4 Hz), 7.39 (2H, d, J=8.1 Hz), 7.32 (2H, d, J=8.7 Hz), 7.23 (2H, d, J=7.8 Hz), 5.22 (2H, s), 4.96 (1H, quint, J=9.0 Hz), 2.32 (3H, s), 2.30-1.60 (8H, m). Purity >90% (NMR) MS 427 (M + 1) Example No. 51 1H NMR (&dgr;) ppm 115 300 MHz, DMSO-d6 8.31 (1H, s), 8.03 (1H, d, J=9.0 Hz), 7.93 (1H, d, J=9.0 Hz), 7.77 (2H, d, J=8.4 Hz), 7.31 (2H, d, J=8.7 Hz), 5.07 (2H, s), 4.94 (1H, quint, J=8.7 Hz), 2.45 (3H, s), 2.26 (3H, s), 2.26-1.60 (8H, m). Purity >90% (NMR) MS 432 (M + 1)

[1867] 8 TABLE 8 Example No. 52 1H NMR (&dgr;) ppm 116 300 MHz, DMSO-d6 12.7 (1H, brs), 10.0 (1H, s), 8.22 (1H, s), 7.87 (1H, d, J=8.6 Hz), 7.69 (1H, d, J=8.6 Hz), 7.53 (2H, d, J=8.6 Hz), 6.96 (2H, d, J=8.6 Hz), 4.89(1H, quint, J=9.0 Hz), 2.30-1.60 (8H, m). Purity >90% (NMR) MS 323 (M + 1) Example No. 53 1H NMR (&dgr;) ppm 117 300 MHz, DMSO-d6 9.18 (1H, t, J=5.6 Hz), 8.34 (1H, s), 8.04 (1H, d, J=9.6 Hz), 7.98 (1H, d, J=8.7 Hz), 7.80 (2H, d, J=8.7 Hz), 7.52-7.32 (7H, m), 5.27 (2H, s), 4.95 (1H, quint, J=9.0 Hz), 3.99 (2H, d, J=5.7 Hz), 2.40-1.60 (8H, m). Purity >90% (NMR) MS 470 (M + 1) Example No. 54 1H NMR (&dgr;) ppm 118 300 MHz, DMSO-d6 8.32 (1H, s), 8.05 (1H, d, J=8.7 Hz), 7.95 (1H, d, J=8.7 Hz), 7.80 (2H, d, J=8.4 Hz), 7.67 (1H, t, J=4.5 Hz), 7.56 (1H, t, J=7.5 Hz), 7.45-7.42 (2H, m), 7.35 (2H, d, J=8.4 Hz), 5.31 (2H, s), 4.96 (1H, quint, J=9.0 Hz), 2.30-1.60 (8H, m). Purity >90% (NMR) MS 447 (M + 1)

[1868] 9 TABLE 9 Example No. 55 1H NMR (&dgr;) ppm 119 300 MHz, DMSO-d6 12.78(1H, brs), 8.24 (1H, s), 7.88 and 7.72 (2H, ABq, J=8.6 Hz), 7.66 and 7.23 (4H, A′ B′ q, J =8.6 Hz), 7.58 (1H, s), 7.48-7.42 (3H, m), 5.24 (1H, s), 4.88 (1H, quint, J=8.8 Hz), 2.30-1.91 (6H, m), 1.78-1.60 (2H, m) Purity 90% (NMR) MS 447 (M + 1) Example No. 56 1H NMR (&dgr;) ppm 120 300 MHz, DMSO 12.89 (1H, broad), 8.18 (1H, s), 7.87 (1H, d, J=8.4 Hz), 7.74 (1H, d, J=9.2 Hz), 7.67 (2H, d, J=8.8 Hz), 7.52 (2H, m), 7.45 (2H, m), 7.38 (1H, m), 7.23 (2H, d, J=8.8 Hz), 5.22 (2H, s), 4.94 (1H, quintet, J=8.9 Hz), 2.16 (4H, m), 1.98 (2H, m), 1.73 (2H, m). Purity >90% (NMR) MS 413 (M+) Example No. 57 1H NMR (&dgr;) ppm 121 300 MHz, DMSO-d6 10.99 (1H, s), 8.26 (1H, s), 8.01-7.86 (4H, m), 7.69-7.59 (5H, m), 7.38 (2H, d, J=8.7 Hz), 4.86 (1H, quint, J=8.7 Hz), 2.12-1.90 (6H, m), 1.72-1.59 (2H, m) Purity >90% (NMR) MS 462 (M + 1)

[1869] 10 TABLE 10 Example No. 58 1H NMR (&dgr;) ppm 122 300 MHz, DMSO-d6 12.78 (1H. s), 10.69 (1H, s), 8.26-7.72 (9H, m), 4.92 (1H, quint, J=9.0 Hz), 2.34-1.70 (6H, m), 1.75-1.61 (2H, m) Purity >90% (NMR) MS 494 (M + 1) Example No. 59 1H NMR (&dgr;) ppm 123 300 MHz, DMSO-d6 10.82 (1H, s), 8.34 (1H, s), 8.14 and 7.84 (4H, ABq, J =8.4 Hz), 8.06 and 7.66 (4H, A′ B′ q, J =8.6 Hz), 8.06-7.98 (4H, m), 5.01 (1H, quint, J=9.3 Hz), 2.35-2.15 (4H, m), 2.11-1.96 (2H, m), 1.80-1.62 (2H, m) Purity >90% (NMR) MS 460 (M + 1) Example No. 60 1H NMR (&dgr;) ppm 124 300 MHz, DMSO-d6 10.61 (1H, s), 8.32 (1H, s), 8.12 and 7.81 (4H, ABq, J=8.9 Hz), 8.03 and 7.93 (2H, A′ B′ q, J=8.7 Hz), 7.95 and 7.59 (4H, A″B″ q, J=8.4 Hz), 4.99 (1H, quint, J=9.0 Hz), 2.33-2.12 (4H, m), 2.10-1.93 (2H, m), 1.80-1.63 (2H, m). 1.34 (9H, m) Purity >90% (NMR) MS 482 (M + 1)

[1870] 11 TABLE 11 Example No. 61 1H NMR (&dgr;) ppm 125 300 MHz, DMSO-d6 10.6 (1H, s), 8.34 (1H, s), 8.13 (2H, d, J=8.7 Hz), 8.09-7.98 (4H, m), 7.82 (2H, d, J=8.7 Hz), 7.50-7.35 (5H, m), 7.20-7.17 (2H, d, J=9.0 Hz), 5.24 (2H, s), 5.01 (1H, quint, J=9.3 Hz), 2.40-1.60 (8H, m). Purity >90% (NMR) MS 532 (M + 1) Example No. 62 1H NMR (&dgr;) ppm 126 300 MHz, DMSO-d6 8.32 (1H, s), 8.26 (1H, d, J=8.7 Hz), 8.04 (1H, d, J=8.7 Hz), 7.77 (2H, d, J=8.4 Hz), 7.52 (2H, d, J=6.9 Hz), 7.46-7.39 (5H, m), 5.28 (2H, s), 4.38 (1H, m), 3.71 (1H, m), 2.60-2.15 (2H, m), 2.04-1.96 (4H, m), 1.30-1.20 (2H, m). Purity >90% (NMR) MS 443 (m + 1) Example No. 63 1H NMR (&dgr;) ppm 127 300 MHz, DMSO-d6 8.27 (1H, s), 8.14 (1H, d, J=8.7 Hz), 7.96 (1H, d, J=8.4 Hz), 7.71 (2H, d, J=9.0 Hz), 7.51 (2H, d, J=6.9 Hz), 7.46-7.37 (3H, m), 7.30 (2H, d, J=8.4 Hz), 5.25 (3H, s), 4.39 (1H, m), 3.44 (1H, m), 3.27 (3H, s), 2.60-1.95 (6H, m), 1.25-1.05(2H, m). Purity >90% (NMR) MS 457 (M + 1)

[1871] 12 TABLE 12 Example No. 64 1H NMR (&dgr;) ppm 128 300 MHz, DMSO-d6 12.25 (1H, brs), 7.70-7.30 (9H, m), 7.20 (2H, d, J=8.7 Hz), 7.14 (1H, d, J=8.4 Hz), 5.20 (2H, s), 4.84 (1H, quint, J=6.0 Hz), 3.66 (2H, s), 2.30-1.51 (8H, m) Purity >90% (NMR) MS 427 (M + 1) Example No. 65 1H NMR (&dgr;) ppm 129 300 MHz, DMSO-d6 12.64 (1H, brs), 8.13 (1H, s), 7.80 (1H, d, J=7.2 Hz), 7.59 (1H, d, J=8.7 Hz), 7.48-7.30 (5H, m), 5.11 (2H, s), 5.03 (1H, quint, J=8.7 Hz), 4.20-4.05 (2H, m), 3.45-3.90 (3H, m), 2.15-1.60 (12H, m) Purity >90% (NMR) MS 448 (M + 1) Example No. 66 1H NMR (&dgr;) ppm 130 300 MHz, DMSO-d6 10.59 (1H, s), 8.31 (1H, s), 8.10 (2H, d, J=8.6 Hz), 8.03 (1H, d, J=8.7 Hz), 8.00-7.85 (3H, m), 7.80 (2H, d, J=8.6 Hz), 7.41 (2H, d, J=8.2 Hz), 4.98 (1H, quint, J=8.8 Hz), 2.71-1.10 (19H, m) Purity >90% (NMR) MS 508 (M + 1)

[1872] 13 TABLE 13 Example No. 67 1H NMR (&dgr;) ppm 131 300 MHz, DMSO-d6 12.81 (1H, brs), 8.42 (1H, s), 7.90 (1H, d, J=8.5 Hz), 7.80-7.52 (6H, m), 7.44 (2H, d, J=8.6 Hz), 5.25 (2H, s), 4.88 (1H, quint, J=8.8 Hz), 2.30-1.52 (8H, m) Purity >90% (NMR) MS 481 (M + 1) Example No. 68 1H NMR (&dgr;) ppm 132 300 MHz, DMSO-d6 8.31 (1H, d, J=1.4 Hz), 8.05 (1H, d, J=8.6 Hz), 7.96 (1H, d, J=8.6 Hz), 8.86-8.61 (4H, m), 7.51 (1H, d, J=6.3 Hz), 7.33 (2H, d, J=8.8 Hz), 5.28 (2H, s), 4.94 (1H, quint, J=8.8 Hz), 2.31-1.60 (8H, m) Purity >90% (NMR) MS 481 (M + 1) Example No. 69 1H NMR (&dgr;) ppm 133 300 MHz, DMSO-d6 9.88 (1H, s), 9.42 (1H, s), 8.32 (1H, s), 8.09 and 8.02 (2H, ABq, J=9.0 Hz), 7.81 and 7.78 (4H, A′ B′ q, J=9.2 Hz), 7.50 (2H, d, J=7.8 Hz), 7.31 (2H, t, J=7.8 Hz), 7.00 (1H, t, J=7.8 Hz), 5.03 (1H, quint, J=8.7 Hz), 2.34-2.17 (4H, m), 2.13-1.96 (2H, m), 1.83-1.64 (2H, m) Purity >90% (NMR) MS 441 (M + 1)

[1873] 14 TABLE 14 Example No. 70 1H NMR (&dgr;) ppm 134 300 MHz, DMSO-d6 8.27 (1H, d, J=1.2 Hz), 8.04 (1H, d, J=8.7 Hz), 7.94 (1H, d, J=8.7 Hz), 7.72 (2H, d, J=8.7 Hz), 7.60-7.20 (12H, m) 6.74 (1H, s), 4.92 (1H, quint, J=8.9 Hz), 2.30-1.58 (8H, m) Purity >90% (NMR) MS 489 (M + 1) Example No. 71 1H NMR (&dgr;) ppm 135 300 MHz, DMSO-d6 8.31 (1H, s), 8.05 (1H, d, J=8.7 Hz), 7.97 (1H, d, J=8.7 Hz), 7.76 (2H, d, J=8.6 Hz), 7.44-7.19 (7H. m), 4.94 (1H, quint, J=8.8 Hz), 4.35 (2H, t, J=6.7 Hz), 3.10 (2H, t, J=6.7 Hz), 2.32-1.60 (8H, m) Purity >90% (NMR) MS 427 (M + 1) Example No. 72 1H NMR (&dgr;) ppm 136 300 MHz, DMSO-d6 8.30 (1H, s), 8.25 (1H, d, J=8.7 Hz), 8.03 (1H, d, J=9.0 Hz), 7.75 (2H, d, J=8.7 Hz), 7.51 (2H, d, J=7.2 Hz), 7.46-7.33 (5H, m), 5.27 (2H, s), 4.36 (1H, m), 2.50-2.25 (2H, m), 2.15-2.00 (2H, m), 1.95-1.85 (2H, m), 1.35 (1H, m), 1.20-1.10 (2H, m), 0.87 (9H, s). Purity >90% (NMR) MS 483 (M + 1)

[1874] 15 TABLE 15 Example No. 73 1H NMR (&dgr;) ppm 137 300 MHz, DMSO-d6 7.59 (2H, d, J=8.4 Hz), 7.52-7.35 (6H, m), 7.20 (2H, d, J=8.7 Hz), 7.14 (1H, d, J=2.1 Hz), 6.90 (m, dd, J=9.0, 2.4 Hz), 5.21 (2H, s), 4.83 (1H, quint, J=8.7 Hz), 4.70 (2H, s), 2.30-1.90 (6H, m), 1.75-1.55 (2H, m). Purity >90% (NMR) MS 443 (M + 1) Example No. 74 1H NMR (&dgr;) ppm 138 300 MHz, DMSO-d6 8.27 (1H, s), 8.06 and 7.97 (2H, ABq, J=8.7 Hz), 7.57 and 6.86 (4H, A′ B′ q, J=8.9 Hz), 7.42-7.26 (5H, m), 5.04(1H, quint, J=9.0 Hz), 4.42 (2H, s), 2.32-1.94 (6H, m), 1.80-1.62 (2H, m) Purity >90% (NMR) MS 412 (M + 1) Example No. 75 1H NMR (&dgr;) ppm 139 300 MHz, DMSO-d6 12.80 (1H, s), 8.26 (1H, s), 7.90 (1H, d, J=9.2 Hz), 7.76-7.60 (8H, m), 7.35 (2H, d, J=8.4 Hz), 4.84 (1H, quint, J=8.8 Hz), 3.23 (3H, s), 2.32-1.90 (6H, m), 1.78-1.61 (2H, m) Purity >90% (NMR) MS 475 (M + 1)

[1875] 16 TABLE 16 Example No. 76 1H NMR (&dgr;) ppm 140 300 MHz, DMSO-d6 8.29 (1H, s), 8.07 and 7.49 (2H, ABq, J=8.7 Hz), 7.66 and 7.00 (4H, A′ B′ q, J=7.7 Hz), 7.39-7.24 (5H, m), 5.05 (1H, quint, J=8.8 Hz), 4.76 (2H, s), 3.21 (3H, s), 2.35-1.92 (6H, m), 1.81-1.62 (2H, m) Purity >90% (NMR) MS 426 (M + 1) Example No. 77 1H NMR (&dgr;) ppm 141 300 MHz, DMSO-d6 8.21 (1H, s), 7.87 (1H, s), 7.56 and 7.43 (4H, ABq, J=8.1 Hz), 7.34-7.16 (5H, m), 4.25 (1h, brt, J=12.5 Hz), 3.06-2.92 (4H, m), 2.41-2.17 (2H, m), 1.96-1.77 (4H, m), 1.72-1.58 (1H, m), 1.48-1.15 (3H, m) Purity >90% (NMR) MS 425 (M + 1) Example No. 78 1H NMR (&dgr;) ppm 142 300 MHz, DMSO-d6 8.14 (1H, s), 7.79 (1H, d, J=9.0 Hz), 7.57 (1H, d, J=8.7 Hz), 7.40-7.20 (5H, m), 4.89 (1H, quint, J=8.7 Hz), 3.54 (2H, s), 3.19-2.90 (3H, m), 2.23-1.69 (14H, m) Purity >90% (NMR) MS 404 (M + 1)

[1876] 17 TABLE 17 Example No. 79 1H NMR (&dgr;) ppm 143 300 MHz, DMSO-d6 8.15 (1H, s), 7.81 (1H, d, J=8.4 Hz), 7.59 (1H, d, J=9.0 Hz), 7.50-7.38 (5H, m), 5.05 (1H, quint, J=9.0 Hz), 3.85-2.95 (3H, m), 2.20-1.65 (14H, m) Purity >90% (NMR) MS 418 (M + 1) Example No. 80 1H NMR (&dgr;) ppm 144 300 MHz, DMSO-d6 8.17 (1H, m), 7.84 (1H, d, J=8.4 Hz), 7.78-7.62 (3H, m), 7.49 (2H, d, J=8.1 Hz), 5.05-4.91 (1H, m), 3.80-3.70 (2H, m), 3.30-3.12 (1H, m), 2.48-2.31 (5H, m), 2.15-1.60 (12H, m) Purity >90% (NMR) MS 468 (M + 1) Example No. 81 1H NMR (&dgr;) ppm 145 300 MHz, DMSO-d6 12.75 (1H, brs), 8.21 (1H, d, J=1.4 Hz), 7.49 (1H, d, J=8.6 Hz), 7.85 (1H, dd, J=8.6, 1.4 Hz), 7.70-7.55 (5H, m), 7.23 (2H, d, J=8.7 Hz), 5.25 (2H, s), 4.36-4.15 (1H, m), 2.39-2.18 (2H, m), 2.00-1.78 (4H, m), 1.70-1.57 (1H, m), 1.48-1.15 (3H, m) Purity >90% (NMR) MS 495 (M + 1)

[1877] 18 TABLE 18 Example No. 82 1H NMR (&dgr;) ppm 146 300 MHz, DMSO-d6 8.27 (1H, s), 8.22 (1H, d, J=8.7 Hz), 8.02 (1H, d, J=8.7 Hz), 7.69 (2H, d, J=8.7 Hz), 7.60-7.50 (4H, m), 7.45-7.25 (8H, m), 6.75 (1H, s), 4.21-4.23 (1H, m), 2.39-2.18 (2H, m), 2.10-1.78 (4H, m), 1.70-1.15 (4H, m) Purity >90% (NMR) MS 503 (M + 1) Example No. 83 1H NMR (&dgr;) ppm 147 300 MHz, DMSO-d6 13.2 (1H, brs), 8.30 (1H, s), 8.23 (1H, d, J=8.8 Hz), 8.02 (1H, d, J=8.7 Hz), 7.74 (2H, d, J=8.6 Hz), 7.40-7.33 (5H, m), 5.22 (2H, s), 4.36 (1H, m), 2.50-1.40 (10H, m), 1.31 (18H, s). Purity >90% (NMR) MS 539 (M + 1) Example No. 84 1H NMR (&dgr;) ppm 148 mixture of isomers (cis:trans = 3:1) 300 MHz, DMSO-d6 8.30 (1H, s), 8.20-7.95 (2H, m), 7.72 (2H, d, J=8.4 Hz), 7.52-7.29 (7H, m), 5.25 (2H, s), 4.34, 3.40 (1H, m), 2.50-2.20 (2H, m), 2.05-1.50 (6H, m), 1.14, 0.90 (3H, d, J=6.9, 6.3 Hz), 1.09 (1H, m). Purity >90% (NMR) MS 441 (M + 1)

[1878] 19 TABLE 19 Example No. 85 1H NMR (&dgr;) ppm 149 300 MHz, DMSO-d6 8.25 (1H, s), 8.14-7.83 (6H, m), 7.77-7.44 (5H, m), 7.21 (2H, d, J=7.8 Hz), 4.44 (2H, brt), 4.31 (1H, brt), 3.56 (2H, brt), 2.20-2.16 (2H, m), 2.00-1.74 (4H, m), 1.70-1.55 (1H, m), 1.45-1.14 (3H, m) Purity >90% (NMR) MS 491 (M + 1) Example No. 86 1H NMR (&dgr;) ppm 150 300 MHz, DMSO-d6 12.75 (1H, s), 8.23 (1H, s), 8.15 (1H, d, J=7.6 Hz), 8.02-7.53 (10H, m), 7.32 (2H, d, J=8.7 Hz), 5.68 (2H, s), 4.32 (1H, brt, J=12.2 Hz), 2.41-2.20 (2H, m), 2.01-1.78 (4H, m), 1.71-1.56 (1H, m), 1.50-1.16 (3H, m) Purity >90% (NMR) MS 477 (M + 1) Example No. 87 1H NMR (&dgr;) ppm 151 300 MHz, DMSO-d6 12.75 (1H, brs), 8.16 (1H, s), 7.91 and 7.82 (2H, ABq, J=8.5 Hz), 7.44 and 6.86 (4H, A′ B′ q, J=8.6 Hz), 7.39-7.26 (10H, m), 4.82 (2H, s), 4.35 (1H, brt, J=12.2 Hz), 2.35-2.16 (2H, m), 1.97-1.75 (4H, m), 1.69-1.56 (1H, m), 1.45-1.16 (3H, m) Purity >90% (NMR) MS 516 (M + 1)

[1879] 20 TABLE 20 Example No. 88 111 NMR(6) ppm 152 300 MHz, DMSO-d6 8.31 (1H, s), 8.26 and 8.06 (2H, ABq, J=8.9 Hz), 7.73 and 7.22 (4H, A′ B′ q, J=8.7 Hz), 7.50-7.36 (8H, m), 5.10 (2H, s), 4.37 (1H, brt, J=12.2 Hz), 2.38-2.28 (2H, m), 2.10-1.80 (4H, m), 1.70-1.56 (1H, m), 1.50-1.20 (3H, m) Purity >90% (NMR) MS 503 (M + 1) Example No. 89 1H NMR (&dgr;) ppm 153 Purity 91% (HPLC) MS 427 (M + 1) Example No. 90 1H NMR (&dgr;) ppm 154 300 MHz, DMSO-d6 8.40-8.20 (2H, m), 8.04 (1H, d, J=8.4 Hz), 7.65 (2H, d, J=8.4 Hz), 7.50-7.10 (12H, m), 5.08 (1H, m), 4.33 (1H, m), 3.00 (4H, m), 2.50-1.10 (10H, m) Purity >90% (NMR) MS 531 (M + 1)

[1880] 21 TABLE 21 Example No. 91 1H NMR (&dgr;) ppm 155 300 MHz, DMSO-d6 8.31 (1H, s), 8.27 (1H, d, J=8.7 Hz), 8.08-8.03 (3H, m), 7.77-7.58 (5H, m), 7.31 (2H, d, J=8.7 Hz), 5.81 (2H, s), 4.40 (1H, m), 2.50-1.20 (10H, m). Purity about 90% (NMR) MS 455 (M + 1) Example No. 92 1H NMR (6) ppm 156 300 MHz, DMSO-d6 11.8 (1H, brs), 8.07 (1H, s), 7.89 (1H, d, J=8.7 Hz), 7.84 (1H, d, J=8.4 Hz), 7.69 (2H, m), 7.48 (3H, m), 4.42 (2H, s), 4.11 (1H, m), 3.73 (4H, m), 3.40 (4H, m), 2.40-1.40 (10H, m). Purity >90% (NMR) MS 419 (M + 1) Example No. 93 1H NMR (&dgr;) ppm 157 300 MHz, DMSO-d6 8.32 (1H, s), 8.28(1H, d, J=8.9 Hz), 8.05 (1H, d, Jp32 8.7 Hz), 7.72 (2H, d, J=8.7 Hz), 7.38 (4H, d, J=7.2 Hz), 7.31 (4H, t, J=7.3 Hz), 7.21-7.17 (4H, m), 4.37 (1H, m), 4.26 (1H, t, J=7.9 Hz), 4.01 (2H, t, J=6.2 Hz), 2.57 (2H, m), 2.50-2.20 (2H, m), 2.10-2.00 (2H, m), 2.00-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.20 (3H, m). Purity >90% (NMR) MS 531 (M + 1)

[1881] 22 TABLE 22 Example No. 94 1H NMR (&dgr;) ppm 158 300 MHz, DMSO-d6 8.32 (1H, s), 8.27 (1H, d, J=9.0 Hz), 8.05 (1H, d, J=8.7 Hz), 7.75-7.70 (3H, m), 7.56 (1H, d, J=8.4 Hz), 7.55-7.35 (6H, m), 7.22 (2H, d, J=8.7 Hz), 5.11 (2H, s), 4.36 (1H, m), 2.40-2.15 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.20 (3H, m). Purity >90% (NMR) MS 537 (M + 1) Example No. 95 1H NMR (&dgr;) ppm 159 300 Hz, DMSO-d6 12.9 (1H, brs), 8.02 (1H, s), 7.82 (2H, m), 7.40-7.25 (5H, m), 4.58 (2H, s), 4.09 (1H, m), 3.71 (1H, m), 3.49 (2H, m), 3.21 (2H, m), 2.35-1.30 (14H, m). Purity >90% (NMR) MS 434 (M + 1) Example No. 96 1H NMR (&dgr;) ppm 160 300 MHz, DMSO-d6 8.31 (1H, d, J=1.3 Hz), 8.27 (1H, d, J=8.8 Hz), 8.05 (1H, d, J=8.8 Hz), 7.76 (2H, d, J=8.7 Hz), 7.40-7.25 (4H, m), 7.06-6.90 (3H, m), 4.53-4.26 (5H, m), 2.40-2.18 (2H, m), 2.12-1.56 (5H, m), 1.50-1.19 (3H, m) Purity >90% (NMR) MS 457 (M + 1)

[1882] 23 TABLE 23 Example No. 97 1H NMR (&dgr;) ppm 161 300 MHz, DMSO-d6 8.32 (1H, d, J=1.3 Hz), 8.29 (1H, d, J=8.8 Hz), 8.05 (1H, dd, J=8.8, 1.3 Hz), 8.42 (2H, d, J=8.8 Hz), 7.37-7.16 (7H, m), 4.48-4.30 (1H, m), 4.12 (2H, t, J=6.2 Hz), 2.83-2.70 (2H, m), 2.40-1.50 (9H, m), 1.59-1.19 (3H, m) Purity >90% (NMR) MS 455 (M + 1) Example No. 98 1H NMR (&dgr;) ppm 162 300 MHz, DMSO-d6 8.28 (1H, d, J=1.3 Hz), 8.21 (1H, d, J=8.8 Hz), 8.01 (1H, d, J=10.1 Hz), 7.70 (2H, d, J=8.7 Hz), 7.33-7.12 (7H, m), 4.44-4.28 (1H, m), 4.10 (2H, t, J=6.3H z), 2.62 (2H, t, J=7.4 Hz), 2.39-2.15 (2H, m), 2.10-1.18 (14H, m) Purity >90% (NMR) MS 483 (M + 1) Example No. 99 1H NMR (&dgr;) ppm 163 300 MHz, DMSO-d6 12.93 (1H, brs), 8.30 (1H, d, J=1.4 Hz), 8.04 (1H, d, J=8.7 Hz), 7.92 (1H, dd, J=8.7, 1.4 Hz), 7.59-7.34 (5H, m), 7.07 (1H, s), 5.38 (2H, s), 4.78-4.60 (1H, m), 2.32-2.14 (2H, m), 2.03-1.28 (8H, m) Purity >90% (NMR) MS 418 (M + 1)

[1883] 24 TABLE 24 Example No. 100 1H NMR (&dgr;) ppm 164 300 MHz, DMSO-d6 8.46 (1H, d, J=2.1 Hz), 8.16 (1H, s), 8.00 (1H, dd, J=8.5, 2.1 Hz), 7.87 (1H, d, J=8.5 Hz), 7.68 (1H, d, J=8.5 Hz), 7.55-7.30 (5H, m), 7.08 (1H, d, J=8.5 Hz), 5.45 (2H, s), 4.25-4.08 (1H, m), 2.39-2.18 (2H, m), 2.00-1.75 (4H, m), 1.70-1.55 (1H. m), 1.45-1.19 (3H, m) Purity >90% (NMR) MS 427 (M + 1) Example No. 101 1H NMR (&dgr;) ppm 165 300 MHz, DMSO-d6 8.33 (1H, s), 8.31 (1H, d, J=6.9 Hz), 8.06 (1H, d, J=8.4 Hz), 7.76 and 7.29 (4H, ABq, J=8.9 Hz), 6.68 (2H, s), 4.37 (1H, m), 4.35 (2H, t, J=7.0 Hz), 3.79 (6H, s), 3.63 (3H, s), 3.04 (2H, t, J=6.9 Hz), 2.30 (2H, m), 2.04 (2H, m), 1.86 (2H, m), 1.65 (1H, m), 1.50-1.15 (3H, m) Purity >90% (NMR) MS 531 (M + 1) Example No. 102 1H NMR (&dgr;) ppm 166 300 MHz, DMSO-d6 12.88 (1H, s), 8.34 (1H, s), 7.86 (1H, d, J=8.5 Hz), 7.73 (1H, d, J=8.5 Hz), 7.63 and 7.23 (4H, ABq, J=8.7 Hz), 7.52-7.35 (5H, m), 5.22 (2H, s), 4.31 (1H, m), 2.39 (2H, m), 1.79 (2H, m), 1.53 (2H, m), 1.31 (2H, m), 1.11 (3H, s), 0.95 (3H, s) Purity >90% (NMR) MS 455 (M + 1)

[1884] 25 TABLE 25 Example No. 103 1H NMR (&dgr;) ppm 167 300 MHz, DMSO-d6 12.79 (1H, brs), 8.22 (2H, s), 8.02-7.78 (4H, m), 7.63-7.42 (6H, m), 7.20-7.09 (2H, m), 4.43 (2H, s), 4.27 (1H, brt, J=12.2 Hz), 3.59 (2H, s), 2.39-2.15 (2H, m), 1.98-1.72 (4H, m), 1.68-1.59 (1H, m), 1.43-1.12 (3H, m) Purity >90% (NMR) MS 491 (M + 1) Example No. 104 1H NMR (&dgr;) ppm 168 300 MHz, DMSO-d6 12.75 (1H, s), 8.23 (1H, s), 7.94 and 7.86 (2H, ABq, J=8.6 Hz), 7.64 and 7.05 (4H, A′ B′ q, J=8.7 Hz) 7.32-7.09 (9H, m), 5.13 (2H, s), 4.28 (1H, brt, J=12.2 Hz), 2.36-2.19 (2H, m), 1.95-1.77 (4H, m), 1.66-1.56 (1H, m), 1.46-1.10 (3H, m) Purity >90% (NMR) MS 519 (M + 1) Example No. 105 1H NMR (&dgr;) ppm 169 300 MHz, DMSO-d6 8.23 (1H, s), 7.94 and 7.87 (2H, ABq, J=8.6 Hz), 7.68 and 7.17 (4H, A′ B′ q, J=8.7 Hz), 7.46-7.33 (6H, m), 6.93 and 6.75 (2H, A″B″q, J=8.2 Hz), 6.82 (1H, s), 5.13 (2H, s), 4.30 (1H, brt, J=12.2 Hz), 2.39-2.18 (2H, m), 1.98-1.77 (4H, m), 1.71-1.59 (1H, m), 1.48-1.20 (3H, m) Purity >90% (NMR) MS 519 (M + 1)

[1885] 26 TABLE 26 Example No. 106 1H NMR (&dgr;) ppm 170 300 MHz, DMSO-d6 12.89 (1H, brs), 9.73 (1H, s), 8.24 (1H, s), 8.03 and 7.91 (2H, ABq, J=8.7 Hz), 7.66 and 7.04 (4H, A′ B′ q, J=8.7 Hz), 7.16-7.03 (3H, m), 6.89 (2H, t, J=9.2 Hz), 4.33 (1H, brt, J=12.2 Hz), 2.40-2.18 (2H, m), 2.00-1.78 (4H, m), 1.70-1.58 (1H, m), 1.50-1.20 (3H, m) Purity >90% (NMR) MS 429 (M + 1) Example No. 107 1H NMR (&dgr;) ppm 171 300 MHz, DMSO-d6 12.98 (1H, brs), 9.82 (1H, brs), 8.27 (1H, s), 8.09 and 7.94 (2H, ABq, J=8.7 Hz), 7.74 and 7.22 (4H, A′ B′ q, J=8.7 Hz), 7.28-7.22 (1H, m), 6.67-6.54 (3H, m), 4.35 (1H, brt, J=12.2 Hz), 2.40-2.20 (2H, m), 2.05-1.80 (4H, m), 1.72-1.59 (1H, m), 1.50-1.21 (3H, m) Purity >90% (NMR) MS 429 (M + 1) Example No. 108 1H NMR (&dgr;) ppm 172 300 MHz, DMSO-d6 8.24 (1H, s), 8.01 and 7.90 (2H, ABq, J=8.7 Hz), 7.65 and 7.03 (4H, A′ B′ q, J=8.7 Hz), 7.32-7.20 (3H, m), 7.08-7.03 (1H, m), 4.32 (1H, brt, J=12.2 Hz), 3.77 (3H, s), 2.36-2.20 (2H, m), 2.00-1.78 (4H, m), 1.71-1.59 (1H, m), 1.44-1.11 (3H, m) Purity >90% (NMR) MS 443 (M + 1)

[1886] 27 TABLE 27 Example No. 109 1H NMR (&dgr;) ppm 173 300 MHz, DMSO-d6 12.75 (1H, s), 8.24 (1H, s), 7.96 and 7.87 (2H, ABq, J=9.0 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.6 Hz), 7.37 (1H, t, J=7.1 Hz), 6.84-6.70 (3H, m), 4.31 (1H, brt, J=12.2 Hz), 3.78 (3H, s), 2.39-2.20 (2H, m), 1.98-1.78 (4H, m), 1.76-1.60 (1H, m), 1.48-1.13 (3H, m) Purity >90% (NMR) MS 443 (M + 1) Example No. 110 1H NMR (&dgr;) ppm 174 300 MHz, DMSO-d6 8.31 (1H, s), 8.26 and 8.04 (2H, ABq, J=8.8 Hz), 7.75 and 7.71 (4H, A′ B′ q, J=8.8 Hz), 7.32-7.03 (4H, m), 4.34 (1H, brt, J=12.2 Hz), 3.94 (2H, t, J=6.3 Hz), 2.40-2.19 (2H, m), 2.11-1.81 (4H, m), 1.72-1.16 (6H, m), 0.71 (3H, t, J=7.3 Hz) Purity >90% (NMR) MS 471 (M + 1) Example No. 111 1H NMR (&dgr;) ppm 175 300 MHz, DMSO-d6 8.22 (1H, s), 7.91 and 7.87 (2H, ABq, J=8.7 Hz), 7.68 and 7.18 (4H, A′ B′ q, J=8.7 Hz), 7.35 (1H, t, J=8.5 Hz), 6.80 (1H, d, J=9.0 Hz), 6.72-6.68 (2H, m), 4.30 (1H, brt, J=12.2 Hz), 3.94 (2H, t, J=6.5 Hz), 2.39-2.18 (2H, m), 1.97-1.58 (7H, m), 1.45-1.20 (3H, m), 0.97 (3H, t, J=7.4 Hz) Purity >90% (NMR) MS 471 (M + 1)

[1887] 28 TABLE 28 Example No. 112 1H NMR (&dgr;) ppm 176 300 MHz, DMSO-d6 12.73 (1H, s), 8.22 (1H, s), 7.94 and 7.85 (2H, ABq, J=9.3 Hz), 7.61 and 7.01 (4H, A′ B′ q, J=8.6 Hz), 7.25-7.00 (4H, m), 5.25 (2H, brs), 4.55 (2H, d, J=6.6 Hz), 4.29 (1H, brt, J=12.2 Hz), 2.38-2.18 (2H, m), 1.96-1.78 (4H, m), 1.70-1.56 (1H, m), 1.67 (3H, s), 1.60 (3H, s), 1.48-1.15 (3H, m) Purity >90% (NMR) MS 497 (M + 1) Example No. 113 1H NMR (&dgr;) ppm 177 300 MHz, DMSO-d6 12.75 (1H, s), 8.23 (1H, s), 7.95 and 7.86 (2H, ABq, J=8.9 Hz), 7.69 and 7.18 (4H, A′ B′ q, J=8.9 Hz), 7.35 (1H, t, J=8.3 Hz), 6.81-6.69 (3H, m), 5.41 (2H, brs), 4.54 (2H, d, J=6.6 Hz), 4.31 (1H, brt, J=12.2 Hz), 2.41-2.18 (2H, m), 1.98-1.76 (4H, m), 1.73 (3H, s), 1.70-1.58 (1H, m), 1.68 (3H, s), 1.45-1.17 (3H, m) Purity >90% (NMR) MS 497 (M + 1) Example No. 114 1H NMR (&dgr;) ppm 178 300 MHz, DMSO-d6 12.73 (1H, s), 8.22 (1H, s), 7.94 and 7.85 (2H, ABq, J=8.4 Hz), 7.60 and 6.99 (4H, A′ B′ q, J=8.6 Hz), 7.29-7.00 (4H, m), 4.29 (1H, brt, J=12.2 Hz), 3.99 (2H, t, J=6.3 Hz), 2.41-2.20 (2H, m), 1.95-1.76 (4H, m), 1.70-1.14 (7H, m), 0.76 (3H, d, J=6.6 Hz) Purity >90% (NMR) MS 499 (M + 1)

[1888] 29 TABLE 29 Example No. 115 1H NMR (&dgr;) ppm 179 300 MHz, DMSO-d6 8.23 (1H, s), 7.93 and 7.87 (2H, ABq, J=8.6 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.6 Hz), 7.35 (1H, t, J=7.8 Hz), 6.82-6.69 (3H, m), 4.30 (1H, brt, J=12.2 Hz), 4.00 (2H, t, J=6.9 Hz), 2.38-2.20 (2H, m), 1.97-1.54 (8H, m), 1.47-1.20 (3H, m), 0.93 (6H, d, J=6.6 Hz) Purity >90% (NMR) MS 499 (M + 1) Example No. 116 1H NMR (&dgr;) ppm 180 300 MHz, DMSO-d6 8.30 (1H, s), 8.25 (1H, d, J=8.9 Hz), 8.03 (1H, d, J=8.8 Hz), 7.68 (2H, d, J=8.8 Hz), 7.24 (2H, d, J=7.2 Hz), 7.19-7.10 (6H, m), 6.94 (2H, t, J=7.2 Hz), 4.34 (1H, m), 4.19 (4H, brs), 3.10 (4H, brs), 2.40-2.15 (2H, m), 2.10-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.20 (3H, m). Purity >90% (NMR) MS 557 (M + 1) Example No. 117 1H NMR (&dgr;) ppm 181 300 MHz, DMSO-d6 12.8 (1H, brs), 8.22 (1H, s), 7.98 (1H, d, J=8.7 Hz), 7.87 (1H, d, J=8.6 Hz), 7.80 (2H, d, J=8.2 Hz), 7.72-7.67 (3H, m), 7.59 (2H, d, J=8.7 Hz), 7.54-7.51 (2H, m), 7.42-7.41 (1H, m), 7.11 (2H, d, J=8.8 Hz), 5.09 (2H, s), 4.27 (1H, m), 2.40-2.15 (2H, m), 2.00-1.75 (4H, m), 1.75-1.55 (1H, m), 1.55-1.15 (3H, m). Purity >90% (NMR) MS 571 (M + 1)

[1889] 30 TABLE 30 Example No. 118 1H NMR (&dgr;) ppm 182 300 MHz, DMSO-d6 13.3 (1H, brs), 8.30 (1H, s), 8.25 (1H, d, J=8.9 Hz), 8.04 (1H, d, J=8.7 Hz), 7.72 (2H, d, J=8.8 Hz), 7.57 (4H, d, J=8.6 Hz), 7.33 (2H, d, J=8.9 Hz), 6.84 (1H, s), 4.33 (1H, m), 2.45-2.10 (2H, m), 2.10-1.95 (2H, m), 1.95-1.70 (2H, m), 1.70-1.55 (1H, m), 1.55-1.15 (3H, m). Purity >90% (NMR) MS 571 (M + 1) Example No. 119 1H NMR (&dgr;) ppm 183 300 MHz, DMSO-d6 8.32-8.30 (2H, m), 8.07-8.03 (1H, m), 7.74 and 6.90 (4H, ABq, J=8.7 Hz), 4.37 (1H, m), 4.31 (2H, t, J—6.8 Hz), 3.74 (3H, s), 3.04 (2H, t, J=6.7 Hz), 2.30 (2H, m), 2.02 (2H, m), 1.86 (2H, m), 1.63 (1H, m), 1.55-1.15 (3H, m) Purity >90% (NMR) MS 471 (M + 1) Example No. 120 1H NMR (&dgr;) ppm 184 300 MHz, DMSO-d6 8.23 (1H, s), 7.99 (1H, d, J=8.7 Hz), 7.88 (1H, d, J=8.4 Hz), 7.61 and 7.16 (4H, ABq, J=8.6 Hz), 7.30-7.22 (2H, m), 7.01 (2H, d, J=8.1 Hz), 6.92 (1H, t, J=7.5 Hz), 4.28 (1H, m), 4.25 (2H, t, J=7.2 Hz), 3.83 (3H, s), 3.07 (2H, t, J=7.1 Hz), 2.28 (2H, m) 2.00-1.75 (4H, m), 1.70-1.55 (1H, m), 1.50-1.15 (3H, m) Purity >90% (NMR) MS 471 (M + 1)

[1890] 31 TABLE 31 Example No. 121 1H NMR(&dgr;) ppm 185 300 MHz, DMSO-d6 12.85(1H, brs), 8.24(1H, s), 8.01(1H, d, J=8.7 Hz), 7.90 (1H, d, J=8.6 Hz), 7.62 and, 7.17(4H, ABq, J=8.7 Hz), 7.24 (1H, m), 6.94(2H, m), 6.82 (1H, m), 4.32(2H, t, J=6.7 Hz), 3.76(3H, s), 3.07(2H, t, J=6.7 Hz), 2.29 (2H, m), 2.00-1.75 (4H, m), 1.70-1.55 (1H, m), 1.50-1.15(3H, m) Purity >90% (NMR) MS 471(M + 1) Example No. 122 1H NMR(&dgr;) ppm 186 300 MHz, DMSO-d6 12.8(1H, brs), 8.22(1H, s), 7.87(2H, m), 7.62(2H, d, J=8.1 Hz), 7.60-7.20 (7H, m), 5.23(2H, s), 4.46(1H, m), 2.50-2.30(2H, m), 1.70-1.40(10H, m). Purity >90% (NMR) MS 441(M + 1) Example No. 123 1H NMR(&dgr;) ppm 187 300 MHz, DMSO-d6 8.24(1H, s), 7.97(1H, d, J=9.0 Hz), 7.87 (1H, d, J=8.4 Hz), 7.65(2H, d, J=8.7 Hz), 7.40-7.05(9H, m), 7.03(2H, d, J=8.4 Hz), 4.31(1H, m), 4.18(2H, t, J=6.6 Hz), 2.81 (2H, t, J=6.3 Hz), 2.40-2.20 (2H, m), 2.00-1.70(4H, m), 1.70-1.50(1H, m), 1.50-1.05(3H, m). Purity >90% (NMR) MS 533(M + 1)

[1891] 32 TABLE 32 Example No. 124 1H NMR(&dgr;) ppm 188 300 MHz, DMSO-d6 13.1(1H, brs), 8.29(1H, s), 8.17(1H, d, J=8.7 Hz), 7.99 (1H, d, J=8.7 Hz), 7.77 (2H, d, J=8.7 Hz), 7.40-7.20 (8H, m), 6.84(1H, d, J=9.3 Hz), 6.75-6.72(2H, m), 4.36(1H, m), 4.22(2H, t, J=6.8 Hz), 3.04 (2H, t, J=6.7 Hz), 2.40-2.15 (2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55 (1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 533(M + 1) Example No. 125 1H NMR(&dgr;) ppm 189 300 MHz, DMSO-d6 8.32(1H, s), 8.28(1H, d, J=8.7 Hz), 8.05(1H, d, J=9.0 Hz), 7.73(2H, d, J=9.0 Hz), 7.43 (4H, d, J=7.2 Hz), 7.36-7.20 (8H, m), 4.74(2H, d, J=7.5 Hz), 4.57(1H, t, J=7.5 Hz), 4.38(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.85 (2H, m), 1.85-1.55(1H, m), 1.55-1.20(3H, m). Purity >90% (NMR) MS 517(M + 1) Example No. 126 1H NMR(&dgr;) ppm 190 300 MHz, DMSO-d6 8.32 (1H, s), 8.14(1H, d, J=8.7 Hz), 8.03(1H, d, J=8.7 Hz), 7.77(2H, d, J=9.0 Hz), 7.52-7.31(7H, m), 5.74(2H, m), 5.26(2H, s), 4.61(1H, m), 2.96 (1H, m), 2.60-2.10(5H, m). 38 Purity >90% (NMR) MS 425(M + 1)

[1892] 33 TABLE 33 Example No. 127 1H NMR(&dgr;) ppm 191 300 MHz, DMSO-d6 13.2(1H, brs), 8.33(1H, s), 8.12(1H, d, J=8.7 Hz), 7.96 (1H, d, J=8.8 Hz), 7.79(2H, d, J=8.7 Hz), 7.52-7.32(7H, m), 5.26(2H, s), 4.92(1H, d, J=49.4 Hz), 4.57(1H, m), 2.65-2.35(2H, m), 2.25-1.50 (6H, m). Purity >90% (NMR) MS 445(M + 1) Example No. 128 1H NMR(&dgr;) ppm 192 300 MHz, DMSO-d6 8.21(1H, s), 7.92 and 7.85 (2H, ABq, J=8.6 Hz), 7.61 and 7.06(4H, A′ B′ q, J=8.6 Hz), 7.36-6.91(9H, m), 4.24(1H, brt, J=12.2 Hz), 2.35-2.15(2H, m), 1.95-1.75(4H, m), 1.70-1.58(1H, m), 1.48-1.14(3H, m) Purity >90% (NMR) MS 505(M + 1) Example No. 129 1H NMR(&dgr;) ppm 193 300 MHz, DMSO-d6 8.21(1H, s), 7.92 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.22(4H, A′ B′ q, J=8.6 Hz), 7.52-7.39(1H, m), 7.47 and 7.41 (2H, A″B″q, J=8.1 Hz), 6.91 (1H, d, J=8.0 Hz), 6.89(1H, d, J=8.2 Hz), 6.75(1H, s,), 4.36-4.18(4H, m), 2.38-2.17(2H, m), 1.95-1.76(4H, m), 1.70-1.59(1H, m), 1.44-1.19(3H, m) Purity >90% (NMR) MS 505(M + 1)

[1893] 34 TABLE 34 Example No. 130 1H NMR(&dgr;) ppm 194 300 MHz, DMSO-d6 8.27(1H, s), 7.69(2H, d, J=8.6 Hz), 7.49-7.21(11H, m), 5.08 and 5.03(2H, ABq, J=12.6 Hz), 5.07-4.99(1H, m) 4.26 (2H, d, J=6.6 Hz), 2.40-2.18 (2H, m), 2.04-1.77(4H, m), 1.70-1.58(1H, m), 1.48-1.15 (3H, m) purity >90% (NMR) MS 590(M + 1) Example No. 131 1H NMR(&dgr;) ppm 195 300 MHz, DMSO-d6 8.29(1H, s), 8.11(1H, d, J=9.0 Hz), 7.96(1H, d, J=8.4 Hz), 7.80(2H, d, J=8.1 Hz), 7.72-7.41(7H, m), 7.12(1H, d, J=12.6 Hz), 7.01(1H, d, J=8.4 Hz), 5.12(2H, s), 4.06(1H, m), 2.35-2.10(2H, m), 2.00-1.75(4H, m), 1.75-1.55(1H, m), 1.60-1.20(3H, m). Purity >90% (NMR) MS 589(M + 1) Example No. 132 1H NMR(&dgr;) ppm 196 300 MHz, DMSO-d6 12.8(1H, brs), 8.23 (1H, s), 7.97(1H, d, J=8.7 Hz), 7.87 (1H, d, J=8.6 Hz), 7.66(2H, d, J=8.6 Hz), 7.49-7.33(5H, m), 7.17-7.05(6H, m), 5.12(2H, s), 4.31(1H, m), 2.40-2.15 (2H, m), 2.05-1.20(8H, m). Purity >90% (NMR) MS 519(M + 1)

[1894] 35 TABLE 35 Example No. 133 1H NMR(&dgr;) ppm 197 300 MHz, DMSO-d6 8.57(1H, s), 8.01(1H, d, J=8.7 Hz), 7.66(1H, d, J=8.7 Hz), 7.51(2H, d, J=8.7 Hz), 7.31 (4H, d, J=8.0 Hz), 7.16(4H, d, J=8.0 Hz), 7.09(2H, d, J=8.7 Hz), 6.26(1H, s), 4.37(1H, m), 2.41-2.28 (2H, m), 2.33 (6H, s), 2.03-1.84(4H, m), 1.77(1H, m), 1.45-1.20(3H, m). Purity >90% (NMR) MS 531(M + 1) Example No. 134 1H NMR(&dgr;) ppm 198 8.59(1H, d, J=1.5 Hz), 8.02 (1H, dd, J=8.7, 1.5 Hz), 7.68 (1H, d, J=8.7 Hz), 7.54(2H, d, J=8.8 Hz), 7.39(4H, dd, J=8.7, 5.3 Hz), 7.08(4H, d, J=8.7 Hz), 7.05(2H, d, J=8.8 Hz), 6.29(1H, s), 4.36(1H, m), 2.43-2.19(2H, m), 2.04-1.85(4H, m), 1.78(1H, m), 1.45-1.23 (3H, m). Purity >90% (NMR) MS 539(M + 1) Example No. 135 1H NMR(&dgr;) ppm 199 300 MHz, DMSO-d6 12.34(1H, brs), 7.93(1H, s), 7.55(1H, d, J=8.6 Hz), 7.33-7.15(6H, m), 7.11(2H, d, J=8.6 Hz), 4.30-4.20(1H, m), 4.07(2H, t, J=6.3 Hz), 3.93 (3H, s), 2.78(2H, t, J=7.4 Hz), 2.35-2.19(2H, m), 2.12-2.00(2H, m), 1.91-1.79(4H, m), 1.69-1.60(1H, m), 1.47-1.20(3H, m) Purity >90% (NMR) MS 485(M + 1)

[1895] 36 TABLE 36 Example No. 136 1H NMR(&dgr;) ppm 200 300 MHz, DMSO-d6 8.13(1H, s), 7.65(2H, d, J=8.7 Hz), 7.63(1H, s), 7.35-7.12(7H, m), 4.35-4.20(1H, m), 4.10(1H, t, J=6.3 Hz), 2.78 (2H, t, J=7.5 Hz), 2.33-1.78 (8H, m), 1.70-1.16(4H, m) Purity >90% (NMR) MS 471(M + 1) Example No. 137 1H NMR(&dgr;) ppm 201 300 MHz, DMSO-d6 8.24(1H, s), 8.11(1H, s), 7.76(2H, d, J=9.0 Hz), 7.37-7.16(7H, m), 4.43-4.30(1H, m), 4.13(2H, t, J=6.3 Hz), 2.84-2.68(5H, m), 2.42-2.22 (2H, m), 2.18-1.80(6H, m), 1.70-1.20(4H, m) Purity >90% (NMR) MS 469(M + 1) Example No. 138 1H NMR(&dgr;) ppm 202 300 MHz, DMSO-d6 12.73(1H, brs), 8.22(1H, s), 7.76(1H, d, J=8.7 Hz), 7.85 (1H, d, J=8.7 Hz), 7.54-7.49 (4H, m), 7.42-7.21 (5H, m), 7.11-7.09(3H, m), 6.93(1H, m), 5.17(2H, s), 4.29 (3H, m), 3.11(2H, m), 2.40-2.20(2H, m), 1.99-1.23(8H, m) Purity >90% (NMR) MS 547(M + 1)

[1896] 37 TABLE 37 Example No. 139 1H NMR(&dgr;) ppm 203 300 MHz, DMSO-d6 12.73(1H, brs), 8.22(1H, s), 7.93(1H, d, J=8.7 Hz), 7.73 (1H, m), 7.60-7.57(2H, m), 7.47-6.90(1H, m), 5.11(2H, s), 4.33-4.28(3H, m), 3.09-3.04(2H, t, J=6.7 Hz), 2.35-2.20(2H, m), 1.95-1.10(8H, m) Purity >90% (NMR) MS 547(M + 1) Example No. 140 1H NMR(&dgr;) ppm 204 300 MHz, DMSO-d6 12.83(2H, brs), 8.22(1H, s), 7.94(1H, d, J=8.7 Hz), 7.85 (1H, d, J=8.4 Hz), 7.63-7.60 (2H, m), 7.26-7.03(6H, m), 4.73(2H, s), 4.30(1H, m), 2.40-2.15(2H, m), 2.00-1.20 (8H, m) Purity >90% (NMR) MS 487(M + 1) Example No. 141 1H NMR(&dgr;) ppm 205 300 MHz, DMSO-d6 12.87(1H, brs), 8.24(1H, s), 7.97(1H, d, J=9.0 Hz), 7.87 (1H, d, J=8.7 Hz), 7.69 and 7.19(4H, ABq, J=8.7 Hz), 7.36 (1H, t, J=8.7 Hz), 6.80-6.72 (3H, m), 4.71(2H, s), 4.32(1H, m), 2.29(2H, m), 1.95-1.25 (8H, m) Purity >90% (NMR) MS 487(M + 1)

[1897] 38 TABLE 38 Example No. 142 1H NMR(&dgr;) ppm 206 300 MHz, DMSO-d6 8.32(1H, s), 8.27(1H, d, J=8.7 Hz), 8.05(1H, d, J=9.0 Hz), 7.76-7.72(3H, m), 7.54(1H, d, J=8.4 Hz), 7.39-7.22(7H, m), 5.11(1H, s), 4.36(1H, m), 2.35(3H, s), 2.35-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 551(M + 1) Example No. 143 1H NMR(&dgr;) ppm 207 300 MHz, DMSO-d6 13.1(1H, brs), 8.30 (1H, s), 8.24(1H, d, J=8.8 Hz), 8.03 (1H, d, J=8.7 Hz), 7.74-7.71 (3H, m), 7.52(1H, d, J=8.3 Hz), 7.40-7.36(3H, m), 7.23(2H, d, J=8.8 Hz), 7.01(2H, d, J=8.7 Hz), 5.11(2H, s), 4.35 (1H, m), 3.79(3H, s), 2.45-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15 (3H, m). Purity >90% (NMR) MS 567(M + 1) Example No. 144 1H NMR(&dgr;) ppm 208 300 MHz, DMSO-d6 13.0 (1H, brs), 8.31 (1H, s), 8.23(1H, d, J=8.7 Hz), 8.04 (1H, d, J=8.7 Hz), 7.80(2H, d, J=8.3 Hz), 7.70-7.66(3H, m), 7.55-7.40(4H, m), 7.03-6.95(2H, m), 5.08(2H, s), 4.03 (1H, m), 2.40-2.15(2H, m), 2.18(3H, s), 2.05-1.70(4H, m), 1.70-1.50(2H, m), 1.50-1.10(3H, m). Purity >90% (NMR) MS 585(M + 1)

[1898] 39 TABLE 39 Example No. 145 1H NMR(&dgr;) ppm 209 300 MHz, DMSO-d6 8.31(1H, s), 8.23(1H, d, J=8.8 Hz), 8.02(1H, d, J=8.7 Hz), 7.73-7.71(3H, m), 7.54(1H, d, J=8.3 Hz), 7.48(2H, d, J=8.4 Hz), 7.41-7.37(3H, m), 7.22(2H, d, J=8.7 Hz), 5.13 (2H, s), 4.34(1H, m), 2.40-2.20 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75(2H, m), 1.70-1.55 (1H, m), 1.50-1.15(3H, m), 1.31(9H, s). Purity >90% (NMR) MS 593(M + 1) Example No. 146 1H NMR(&dgr;) ppm 210 300 MHz, DMSO-d6 8.29(1H, s), 8.13(1H, d, J=8.7 Hz), 7.97(1H, d, J=8.6 Hz), 7.76(1H, d, J=2.1 Hz), 7.63 (1H, t, J=8.5 Hz), 7.57(1H, dd, J=8.2, 2.2 Hz), 7.55-7.35 (6H, m), 7.15(1H, d, J=12.1 Hz), 7.02(1H, d, J=8.6 Hz), 5.10(2H, s), 4.07(1H, m), 2.35-2.10(2H, m), 2.00-1.70 (4H, m), 1.70-1.55 (1H, m), 1.50-1.15(3H, m). Purity >90% (NMR) MS 555(M + 1) Example No. 147 1H NMR(&dgr;) ppm 211 300 MHz, CDCl3 8.61(1H, s), 8.04(1H, d, J=8.7 Hz), 7.69(1H, d, J=8.7 Hz), 7.66(1H, d, J=2.4 Hz), 7.59 (2H, d, J=8.7 Hz), 7.42(1H, d, J=8.0, 2.4 Hz), 7.38(1H, t, J=1.8 Hz), 7.28(2H, d, J=1.8 Hz), 7.26(1H, d, J=8.0 Hz), 7.03(2H, d, J=8.7 Hz), 4.94 (2H, s), 4.37(1H, m), 2.43-2.21(2H, m), 2.17-1.86(4H, m), 1.79(1H, m), 1.43-1.26(3H, m). Purity >90% (NMR) MS 605(M + 1)

[1899] 40 TABLE 40 Example No. 148 1H NMR(&dgr;) ppm 212 300 MHz, DMSO-d6 8.21(s, 1H), 7.89(1H, d, J=8.7 Hz), 7.87(1H, d, J=8.7 Hz), 7.63-7.46(5H, m), 7.30-7.12(5H, m), 7.08(1H, d, J=11.0 Hz), 6.81(1H, s), 3.92(1H, m), 2.15-2.06(2H, m), 1.89-172(4H, m), 1.61(1H, m), 1.42-1.09(3H, m). Purity >90% (NMR) MS 557(M + 1) Example No. 149 1H NMR(&dgr;) ppm 213 300 MHz, DMSO-d6 8.24(1H, d, J=1.5 Hz), 7.96 (1H, d, J=9.0 Hz), 7.88(1H, dd, J=9.0, 1.5 Hz), 7.58(1H, d, J=8.7 Hz), 7.50-7.30(5H, m), 7.22-7.00(6H, m), 5.13(2H, s), 3.98-3.80(1H, s), 2.36-1.10(10H, m) Purity >90%(NMR) MS 553(M + 1) Example No. 150 1H NMR(&dgr;) ppm 214 300 MHz, DMSO-d6 8.23(1H, s), 8.95(1H, d, J=8.4 Hz), 7.88(1H, d, J=8.7 Hz), 7.66(1H, d, J=8.4 Hz), 7.52-7.28(7H, m), 7.23(2H, d, J=9.3 Hz), 7.14(2H, d, J=8.7 Hz), 5.14(2H, s), 3.90-3.72(1H, m), 2.20-1.10(10H, m) Purity >90%(NMR) MS 587(M + 1)

[1900] 41 TABLE 41 Example No. 151 1H NMR(&dgr;) ppm 215 300 MHz, DMSO-d6 8.18(1H, s), 7.92-7.78 (3H, m), 7.78-7.58 (3H, m), 7.58-7.44(4H, m) 7.29(1H, d, J=8.2 Hz), 7.01(2H, d, J=8.7 Hz), 4.88(1H, d, J=11.8 Hz), 4.80(1H, d, J=11.8 Hz), 4.22 (1H, m), 2.37-2.16 (2H, m), 1.95-1.75(4H, m), 1.64(1H, m), 1.48-1.14(3H, m). Purity >90% (NMR) MS 605(M + 1) Example No. 152 1H NMR(&dgr;) ppm 216 300 MHz, DMSO-d6 8.21(2H, m), 7.99-7.80 (2H, m), 7.63-7.08(9H, m), 4.20-3.98(4H, m), 2.20-2.15(2H, m), 1.95-1.74(4H, m), 1.70-1.54(1H, m), 1.44-1.14(3H, m) Purity >90% (NMR) MS 456(M + 1) Example No. 153 1H NMR(&dgr;) ppm 217 300 MHz, DMSO-d6 8.20(1H, s), 8.93 and 7.83(2H, ABq, J=8.7 Hz), 7.86-7.21 (11H, m), 7.03(2H, d, J=8.7 Hz), 4.20(1H, brt, J=12.2 Hz), 2.32-2.13(2H, m), 1.92-1.74(4H, m), 1.69-1.58(1H, m), 1.45-1.15(3H, m) Purity >90% (NMR) MS 489(M + 1)

[1901] 42 TABLE 42 Example No. 154 1H NMR(&dgr;) ppm 218 300 MHz, DMSO-d6 8.23(1H, s), 7.94 and 7.86(2H, ABq, J=8.6 Hz), 7.72-7.16(13H, m), 5.25 (2H, brs), 4.55(2H, d, J=6.6 Hz), 4.31 (1H, brt, J=12.2 Hz), 2.37-2.18 (2H, m), 1.98-1.77(4H, m), 1.70-1.58(1H, m), 1.48-1.20(3H, m) Purity >90% (NMR) MS 489 (M + 1) Example No. 155 1H NMR(&dgr;) ppm 219 300 MHz, DMSO-d6 8.21(1H, s), 7.85 and 7.61(2H, ABq, J=8.7 Hz), 7.6 1 and 6.99(4H, A′ B′ q, J=8.7 Hz), 7.28-7.18(1H, m), 7.25(2H, d, J=7.5 Hz), 7.07-6.99 (1Hm), 4.30(1H, brt, J=12.2 Hz), 3.83(2H, d, J=6.0 Hz), 3.82-3.72(1H, m), 2.68-2.49(2H, m), 2.39-2.21(2H, m), 1.95-1.80(4H, m), 1.79-1.60(2H, m), 1.46-1.22(5H, m), 1.30(9H, s), 1.00-0.82(2H, m) Purity >90% (NMR) MS 626(M + 1) Example No. 156 1H NMR(&dgr;) ppm 220 300 MHz, DMSO-d6 8.22(1H, s), 7.92 and 7.86(2H, ABq, J=8.7 Hz), 7.68 and 7.18(4H, A′ B′ q, J=8.7 Hz), 7.35 (1H, t, J=8.5 Hz), 6.80 (1H, d, J=8.3 Hz), 6.72-6.70(2H, m) 4.30(1H, brt, J=12.2 Hz), 3.99(2H, brd, J=12.0 Hz), 3.85(2H, d, (2H, d, J=6.3 Hz), 2.82-2.62 (2H, m), 2.38-2.20(2H, m), 1.99-1.59 (8H, m), 1.42-1.03(5H, m), 1.39(9H, s) Purity >90% (NMR) MS 626(M + 1)

[1902] 43 TABLE 43 Example No. 157 1H NMR(&dgr;) ppm 221 300 MHz, DMSO-d6 12.78(1H, brs), 8.22 (1H, s), 7.96(1H, d, J=8.6 Hz), 7.86 (1H, d, J=8.6 Hz), 7.75(1H, d, J=2.2 Hz), 7.60(2H, d, J=8.4 Hz), 7.55(1H, dd, J=8.3, 2.2 Hz), 7.48(1H, d, J=8.3 Hz), 7.18(2H, d, J=8.4 Hz), 6.73 (2H, s), 5.08(2H, s), 4.23(1H, m), 3.68(9H, s), 2.37-2.17 (2H, m), 1.99-1.79(4H, m), 1.65(1H, s), 1.49-1.15 (3H, m). Purity >90% (NMR) MS 627(M + 1) Example No. 158 1H NMR(&dgr;) ppm 222 300 MHz, DMSO-d6 12.75(1H, brs), 8.22 (1H, s), 7.93 (2H, d, J=8.7 Hz), 7.85 (2H, d, J=8.5 Hz), 7.53-7.21 (10H, m), 6.94(2H, d, J=8.7 Hz), 4.30-4.12(3H, m), 3.05 (2H, m), 2.35-2.15(2H, m), 1.95-1.75(4H, m), 1.75-1.55 (1H, m), 1.50-1.10(3H, m) Purity >90% (NMR) MS 517(M + 1) Example No. 159 1H NMR(&dgr;) ppm 223 300 MHz, DMSO-d6 12.77(1H, brs), 8.22(1H, s), 7.95(1H, d, 8.6 Hz), 7.86(1H, d, 8.6 Hz), 7.80(1H, s), 7.70-7.35(10H, m), 7.27 (2H, d J=8.7 Hz), 5.30(2H, s), 4.28(1H, m), 2.35-2.15 (2H, m), 1.95-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m) Purity >90% (NMR) MS 503(M + 1)

[1903] 44 TABLE 44 Example No. 160 1H NMR(&dgr;) ppm 224 300 MHz, DMSO-d6 8.90(1H, brs), 8.59(1h, brs), 8.33(1H, s), 8.18 and 8.00 (2H, ABq, J=8.5 Hz), 7.73 and 7.10(4H, A′ B′ q, J=8.5 Hz), 7.32-7.05 (4H, m), 4.35(1H, brt, J=12.2 Hz), 3.86(2H, d, J=6.3 Hz), 3.25-3.08 (2H, m), 2.85-2.66(2H, m), 2.40-2.28(2H, m), 2.07-1.14(15H, m) Purity >90% (NMR) MS 526(M + 1) Example No. 161 1H NMR(&dgr;) ppm 225 300 MHz, DMSO-d6 9.05(1H, brs), 8.76(1h, brs), 8.31(1H, s), 8.19 and 8.00 (2H, ABq, J=8.3 Hz), 7.79 and 7.25 (4H, A′ B′ q, J=8.3 Hz), 7.39(1H, brs), 6.86-6.74(4H, m), 4.37(1H, brt, J=12.2 Hz), 3.89(2H, d, J=5.0 Hz), 3.35-3.18(2H, m), 2.98-2.75(2H, m), 2.38-2.17(2H, m), 2.16-1.15(15H, m) Purity >90% (NMR) MS 526(M + 1) Example No. 162 1H NMR(&dgr;) ppm 226 300 MHz, DMSO-d6 12.87(1H, brs), 8.58(1H, d, J=6.0 Hz), 8.23(1H, s), 7.99 and 7.80(2H, ABq, J=8.6 Hz), 7.61 and 7.18 (4H, A′ B′ q, J=8.0 Hz), 7.45-7.30(5H, m), 5.29 (1H, brs), 4.26(1H, brt, J=12.2 Hz), 2.37-2.11 (2H, m), 2.00-1.71 (4H, m), 1.92 (3H, s), 1.70-1.52(1H, m), 1.45-1.11(3H, m) Purity >90% (NMR) MS 498(M + 1)

[1904] 45 TABLE 45 Example No. 163 1H NMR(&dgr;) ppm 227 300 MHz, DMSO-d6 8.23 (1H, s), 7.95 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.18 (4H, A′ B′ q, J=8.6 Hz), 7.35(1H, t, J=8.6 Hz), 6.80(1H, d, J=7.5 Hz), 6.72-6.69 (2H, m), 5.20(1H, t, J=1.7 Hz), 4.31(1H, brt, J=12.2 Hz), 3.95 2H, t, J=6.8 Hz), 2.49-2.19 (4H, m), 1.97-1.76 (4H, m), 1.68(3H, s), 1.67-1.54(1H, m), 1.61(3H, s), 1.45-1.20 (3H, m) Purity >90% (NMR) MS 511(M + 1) Example No. 164 1H NMR(&dgr;) ppm 228 300 MHz, DMSO-d6 8.20(1H, s), 7.87(2H, s), 7.68 and 7.18(4H, ABq, 18.7 Hz), 7.35(1H, t, J=7.9 Hz), 6.81 (1H, d, J=9.4 Hz), 6.72(1Hs), 6.71(1H, d, J=6.8 Hz), 4.80 (2H, s), 4.29(1H, brt, J=12.2 Hz), 4.10 (1H, t, J=6.7 Hz), 2.43(1H, t, J=6.7 Hz), 2.39-2.19(2H, m), 1.97-1.78(4H, m), 1.76(3H, s), 1.70-1.56 (1H, m), 1.43-1.19(3H, m) Purity >90% (NMR) MS 497(M + 1) Example No. 165 1H NMR(&dgr;) ppm 229 300 MHz, DMSO-d6 11.21(1H, brs), 8.33(1H, s), 8.25(1H, d, J=8.6 Hz), 8.04 (1H, d, J=8.6 Hz), 7.78(2H, d, J=8.7 Hz), 7.70-7.67(2H, m), 7.55-7.42(3H, m), 7.27(2H, d, J=8.7 Hz), 4.73-4.30(5H, m), 4.20-3.97(2H, m), 3.42-3.10(2H, m), 2.45-1.23(14H, m) Purity >90% (NMR) MS

[1905] 46 TABLE 46 Example No. 166 1H NMR(&dgr;) ppm 230 300MHz, DMSO-d6 8.27(1H, s), 8.13(1H, d, J=8.4Hz), 7.97(1H, d, J=9.0Hz), 7.73(1H, d, J=1.8Hz), 7.68(2H, d, J=8.4Hz), 7.54(1H, dd, J=8.4, 2.1Hz), 7.41-7.31(5H, m), 7.19(2H, d, J=8.4Hz), 5.10(2H, s), 4.32(1H, m), 2.50(3H, s), 2.40-2.15(2H, m), 2.10-1.75(4H, m), 1.75-1.55(1H, m), 1.55-1.10(3H, m). Purity >90% (NMR) MS 583(M + 1) Example No. 167 1H NMR(&dgr;) ppm 231 300MHz, DMSO-d6 8.25(1H, s), 8.09(1H, d, J=8.4Hz), 8.00(2H, d, J=8.4Hz), 7.94(1H, d, J=8.7Hz), 7.80(1H, d, J=2.1Hz), 7.73(2H, d, J=8.1Hz), 7.65(2H, d, J=8.7Hz), 7.60(1H, dd, J=8.1, 2.1Hz), 7.44(1H, d, J=8.1Hz), 7.16(2H, d, J=8.7Hz), 5.13(2H, s), 4.30(1H, m), 3.26(3H, s), 2.40-1.15(2H, m), 2.05-1.75(4H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 615(M + 1) Example No. 168 1H NMR(&dgr;) ppm 232 300MHz, DMSO-d6 13.1(1H, brs), 8.32(1H, s), 8.28(1H, d, J=8.8Hz), 8.05(1H, d, J=8.7Hz), 7.80-7.75(3H, m), 7.69(1H, d, J=4.1Hz), 7.57(2H, m), 7.34-7.29(3H, m), 7.20-7.15(1H, m), 5.24(2H, s), 4.39(1H, m), 2.45-2.20(2H, m), 2.20-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 543(M + 1)

[1906] 47 TABLE 47 Example No. 169 1H NMR(&dgr;) ppm 233 300MHz, DMSO-d6 8.31(1H, s), 8.26(1H, d, J=8.7Hz), 8.05(1H, d, J=8.7Hz), 7.78-7.71(3H, m), 7.59-7.41(6H, m), 7.23(2H, d, J=9.0Hz), 5.11(2H, s), 4.35(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 571(M + 1) Example No. 170 1H NMR(&dgr;) ppm 234 300MHz, DMSO-d6 12.7(1H, brs), 8.66(1H, s), 8.61(1H, m), 8.21(1H, s), 7.92-7.79(4H, m), 7.61-7.56(3H, m), 7.50-7.43(2H, m), 7.10(2H, d, J=8.7Hz), 5.09(2H, s), 4.26(1H, m), 2.40-2.15(2H, m), 2.00-1.75(4H, m), 1.75-1.55(1H, m), 1.50-1.15(3H, m). Purity >90% (NMR) MS 538(M + 1) Example No. 171 1H NMR(&dgr;) ppm 235 300MHz, DMSO-d6 8.31(1H, s), 8.25(1H, d, J=8.7Hz), 8.04(1H, d, J=8.7Hz), 7.74-7.71(3H, m), 7.57-7.46(3H, m), 7.39(1H, d, J=8.1Hz), 7.31-7.21(4H, m), 5.11(2H, s), 4.35(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 555(M + 1)

[1907] 48 TABLE 48 Example No. 172 1H NMR(&dgr;) ppm 236 300MHz, DMSO-d6 8.24(1H, s), 7.99(1H, d, J=8.7Hz), 7.88(1H, d, J=10.5Hz), 7.70(1H, dd, J=11.4, 1.8Hz), 7.48-7.32(6H, m), 7.17-7.09(5H, m), 5.12(2H, s), 4.30(1H, m), 2.40-2.15(2H, m), 2.05-1.75(4H, m), 1.75-1.55(1H, m), 1.55-1.20(3H, m). Purity >90% (NMR) MS 537(M + 1) Example No. 173 1H NMR(&dgr;) ppm 237 300MHz, DMSO-d6 8.33(1H, s), 8.29(1H, d, J=8.7Hz), 8.06(1H, d, J=8.7Hz), 7.82-7.74(4H, m), 7.45(1H, dd, J=8.4, 3.0Hz), 7.39(2H, d, J=8.7Hz), 5.28(2H, s), 4.40(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 540(M + 1) Example No. 174 1H NMR(&dgr;) ppm 238 300MHz, DMSO-d6 12.80(1H, brs), 8.26(1H, s), 8.01(1H, d, J=8.7Hz), 7.85(1H, d, J=8.7Hz), 7.80-7.70(1H, m), 7.60-7.36(7H, m), 7.18-6.91(2H, m), 5.09(2H, s), 4.11-3.90(1H, m), 2.32-1.18(14H, m) Purity >90% (NMR) MS 590(M + 1)

[1908] 49 TABLE 49 Example No. 175 1H NMR(&dgr;) ppm 239 300MHz, DMSO-d6 12.75(1H, s), 8.21(1H, s), 7.94 and 7.85(2H, ABq, J=8.7Hz), 7.61 and 7.00(4H, A′ B′ q, J=8.5Hz), 7.31-6.91(2H, m), 7.25(2H, d, J=7.7Hz), 5.41(2H, brs), 4.54(2H, d, J=6.6Hz), 4.35-4.14(2H, m), 2.49-2.15(3H, m), 1.95-1.55(5H, m), 1.50-1.13(5H, m), 1.10-0.77(2H, m) Purity >90% (NMR) MS 568(M + 1) Example No. 176 1H NMR(&dgr;) ppm 240 300MHz, DMSO-d6 8.24(1H, s), 7.97 and 7.87(2H, ABq, J=8.6Hz), 7.69 and 7.19(4H, A′ B′ q, J=8.6Hz), 7.35(1H, t, J=8.1Hz), 6.81(1H, d, J=9.2Hz), 6.72(1H, s), 6.71(1H, d, J=6.5Hz), 4.48-4.20(2H, m), 3.95-3.75(3H, m), 3.03(1H, t, J=12.3Hz), 2.60-2.40(1H, m), 2.39-2.15(2H, m), 2.07-1.58(6H, m), 1.99(3H, s), 1.50-1.00(5H, m) Purity >90% (NMR) MS 568(M + 1) Example No. 177 1H NMR(&dgr;) ppm 241 300MHz, DMSO-d6 12.76(1H, s), 8.23(1H, s), 7.96 and 7.86(2H, ABq, J=8.6Hz), 7.69 and 7.20(4H, A′ B′ q, J=8.6Hz), 7.39(1H, t, J=8.2Hz), 6.86(1H, d, J=8.3Hz), 6.81(1H, s), 6.76(1h, d, J=8.0Hz), 4.83(2H, s), 4.31(1H, brt, J=12.2Hz), 2.39-2.19(2H, m), 1.99-1.79(4H, m), 1.70-1.58(1H, m), 1.48-1.20(3H, m) Purity >90% (NMR) MS 467(M + 1)

[1909] 50 TABLE 50 Example No. 178 1H NMR(&dgr;) ppm 242 300MHz, DMSO-d6 12.85(1H, s), 8.75(1H, s), 8.63(2H, d, # J=3.8Hz), 8.25(1H, s), 8.04-8.01(2H, m), 8.02 and 7.90(2H, ABq, J=8.6Hz), 7.72 and 7.20(4H, A′ B′ q, J=8.6Hz), 7.57(2H, dd, J=7.8, 5.0Hz), 7.40(1H, t, J=8.2Hz), 6.93(1H, d, J=8.2Hz), 6.87(1H, s), 6.77(1H, d, J=8.2Hz), 5.23(2H, s), 4.33(1H, brt, J=12.2Hz), 2.40-2.18(2H, m), 2.00-1.55(5H, m), 1.50-1.15(3H, m) Purity >90% (NMR) MS 520(M + 1) Example No. 179 1H NMR(&dgr;) ppm 243 300MHz, DMSO-d6 8.32(1H, s), 8.29(1H, d, J=9.0Hz), 8.06(1H, d, J=8.7Hz), 7.61(1H, d, J=8.4Hz), 7.58-7.32(5H, m), 6.98(1H, d, J=2.1Hz), 6.93(1H, dd, J=8.7, 2.1Hz), 5.27(2H, s), 4.16-4.00(1H, m), 3.87(3H, s), 2.20-2.12(2H, m), 2.02-1.98(4H, m), 1.70-1.60(1H, m), 1.52-1.10(3H, m) Purity >90% (NMR) MS 457(M + 1) Example No. 180 1H NMR(&dgr;) ppm 244 300MHz, DMSO-d6 8.21(1H, s), 7.91(1H, d, J=8.6Hz), 7.85(1H, d, J=8.6Hz), 7.63(2H, d, J=8.4Hz), 7.60(1H, d, J=9.0Hz), 7.25(2H, d, J=8.4Hz), 7.23(1H, d, J=3.0Hz), 6.95(1H, dd, J=9.0, 3.0Hz), 5.19(2H, d), 4.30(1H, m), 3.78(3H, s), 2.40-2.19(2H, m), 2.00-1.87(4H, m), 1.66(1H, m), 1.49-1.18(3H, m). Purity >90% (NMR) MS 536(M + 1)

[1910] 51 TABLE 51 Example No. 181 1H NMR(&dgr;) ppm 245 300MHz, DMSO-d6 8.19(1H, s), 7.95(1H, d, J=8.7Hz), 7.86(1H, d, J=8.7Hz), 7.65(4H, d, J=7.4Hz), 7.47(2H, d, J=8.7Hz), 7.44-7.27(6H, m), 6.99(2H, d, J=8.7Hz), 4.20(1H, m), 2.34-2.12(2H, m), 1.98-1.75(4H, m), 1.64(1H, m), 1.46-1.13(3H, m). Purity >90% (NMR) MS 547(M + 1) Example No. 182 1H NMR(&dgr;) ppm 246 300MHz, DMSO-d6 8.55(1H, d, J=2.1Hz), 8.32(1H, m), 8.21(1H, s), 7.95(1H, d, J=8.4Hz), 7.86(1H, d, J=7.8Hz), 7.68-7.56(7H, m), 7.14(2H, d, J=8.7Hz), 5.21(1H, s), 4.26(1H, m), 2.35-2.15(2H, m), 2.00-1.75(4H, m), 1.74-1.55(1H, m), 1.50-1.15(3H, m) Purity >90% (NMR) MS 582(M+) Example No. 183 1H NMR(&dgr;) ppm 247 300MHz, DMSO-d6 10.16(1H, s), 8.25(1H, s), 8.07(1H, d, J=8.7Hz), 7.94-7.87(2H, m), 7.71-7.62(3H, m), 7.50-7.42(4H, m), 7.30(1H, d, J=8.4Hz), 7.14(2H, d, J=8.4Hz), 5.06(2H, s), 4.31(1H, m), 2.35-2.15(2H, m), 2.05-1.75(4H, m), 1.75-1.55(1H, m), 1.50-1.15(3H, m) Purity >90% (NMR) MS 594(M+)

[1911] 52 TABLE 52 Example No. 184 1H NMR(&dgr;) ppm 248 300MHz, DMSO-d6 13.2(2H, brs), 8.30(1H, s), 8.26(1H, # d, J=8.8Hz), 8.04(1H, d, J=8.8Hz), 8.00(2H, d, J=8.2Hz), 7.79(1H, s), 7.73(2H, d, J=8.7Hz), 7.61-7.56(3H, m), 7.44(1H, d, J=8.3Hz), 7.23(2H, d, J=8.8Hz), 5.13(2H, s), 4.35(1H, m), 2.45-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(1H, m), 1.75-1.15(3H, m). Purity >90% (NMR) MS 581(M + 1) Example No. 185 1H NMR(&dgr;) ppm 249 300MHz, DMSO-d6 8.30(1H, m), 8.24(1H, d, J=9.0Hz), 8.03(1H, d, J=9.0Hz), 7.79-7.10(9H, m), 5.20-5.07(2H, m), 4.43-4.04(4H, m), 3.50-3.36(2H, m), 2.40-1.19(14H, m) Purity >90% (NMR) MS 554(M + 1) Example No. 186 1H NMR(&dgr;) ppm 250 (DMSO-d6) &dgr;: 8.29(1H, brs), 8.10(1H, d, J=8.4Hz), 7.97(1H, d, J=8.4Hz), 7.79(2H, d, J=8.4Hz), 7.74-7.67(1H, # m), 7.68(2H, d, J=8.4Hz), 7.61(1H, d, J=8.4Hz), 7.57-7.50(2H, m), 7.46-7.39(1H, m), 7.29(1H, d, J=2.4Hz), 7.11(1H, dd, J=2.4, 8.4Hz), 5.12(2H, s), 3.99-3.84(1H, m), 2.35-1.72(6H, m), 1.68-1.55(1H, m), 1.42-1.10(3H, m) Purity >90% (NMR) MS 605(M + 1)

[1912] 53 TABLE 53 Example No. 187 1H NMR(&dgr;) ppm 251 300MHz, DMSO-d6 12.76(1H, s), 8.57(1H, d, J=4.4Hz), 8.23(1H, s), 7.96 and 7.86(2H, ABq, J=8.2Hz), 7.87-7.82(1H, m), 7.68 and 7.12(4H, # A′ B′ q, J=8.6Hz), 7.53(2H, d, J=7.8Hz), 7.37(1H, t, J=8.3Hz), 7.36-7.33(1H, m), 6.90(1H, d, J=8.3Hz), 6.83(1H, s), 6.74(1H, d, J=8.0Hz), 5.20(2H, s), 4.31(1H, brt, J=12.2Hz), 2.35-2.19(2H, m), 1.99-1.57(5H, m), 1.45-1.20(3H, m) Purity >90% (NMR) MS 520(M + 1) Example No. 188 1H NMR(&dgr;) ppm 252 300MHz, DMSO-d6 12.77(1H, brs), 8.21(1H, d, J=1, 4Hz), 7.92(1H, d, J=8.7Hz), 7.88(1H, dd, J=8.7, 1.4Hz), 7.57(2H, d, J=8.7Hz), 7.57-7.27(7H, m), 7.11(2H, d, J=8.7Hz), 5.07(2H, s), 4.26(1H, m), 2.36-2.16(2H, m), 1.98-1.75(4H, m), 1.64(1H, m), 1.49-1.17(3H, m). Purity >90% (NMR) MS 555(M + 1) Example No. 189 1H NMR(&dgr;) ppm 253 300MHz, DMSO-d6 8.32(1H, s), 8.30-8.20(2H, m), 8.10-7.98(2H, m), 7.74(2H, d, J=9.0Hz), 7.60-7.46(5H, m), 7.24(2H, d, J=9.0Hz), 5.19(2H, s), 4.44-4.30(1H, m), 2.40-2.20(2H, m), 2.12-1.78(4H, m), 1.72-1.58(4H, m) Purity >90% (NMR) MS 581(M + 1)

[1913] 54 TABLE 54 Example No. 190 1H NMR(&dgr;) ppm 254 300MHz, DMSO-d6 8.36-7.90(5H, m), 7.74(2H, d, J=8.6Hz), 7.60-7.40(5H, m), 7.25(2H, d, J=8.7Hz), 5.14(2H, s), 4.45-4.28(1H, m), 2.40-2.15(4H, m), 1.75-1.55(1H, m), 1.55-1.20(3H, m) Purity >90% (NMR) MS 580(M + 1) Example No. 191 1H NMR(&dgr;) ppm 255 300MHz, DMSO-d6 8.22(1H, s), 7.94(1H, d, J=8.4Hz), 7.85(1H, d, J=8.7Hz), 7.61(2H, d, J=8.7Hz), 7.25-7.00(6H, m), 4.86(2H, s), 4.30(1H, m), 2.89(3H, s), 2.80(3H, s), 2.29(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m) Purity >90% (NMR) MS 514(M + 1) Example No. 192 1H NMR (&dgr;) ppm 256 300MHz, DMSO-d6 8.22(1H, s), 7.94(1H, d, J=8.4Hz), 7.85(1H, d, J=8.7Hz), 7.61(2H, d, J=8.7Hz), 7.26-7.01(6H, m), 4.84(2H, s), 4.31(1H, m), 3.36(4H, m), 2.29(2H, m), 2.00-1.75(4H, m), 1.75-1.15(10H, m) Purity >90% (NMR) MS 554(M + 1)

[1914] 55 TABLE 55 Example No. 193 1H NMR(&dgr;) ppm 257 300MHz, DMSO-d6 13.00(1H, brs), 8.29(1H, d, J=1.4Hz), 8.15(1H, d, J=8.8Hz), 7.97(1H, dd, J=1.4Hz, 8.8Hz), 7.89(2H, d, J=8.8Hz), 7.80-7.60(5H, m) 7.25(2H, d, J=8.8Hz), 4.47-3.90(4H, m), 3.20-3.10(2H, m), 2.41-1.22(14H, m) Purity >90% (NMR) MS 560(M + 1) Example No. 194 1H NMR(&dgr;) ppm 258 300MHz, DMSO-d6 12.80(1H, brs), 8.23(1H, s), 7.97(1H, d, J=8.5Hz), 7.87(1H, d, J=8.5Hz), 7.70-7.17(9H, m), 4.60-4.13(4H, m), 3.72-3.40(2H, m), 2.40-1.15(14H, m) Purity >90% (NMR) MS 524(M + 1) Example No. 195 1H NMR(&dgr;) ppm 259 300MHz, DMSO-d6 8.25(1H, s), 8.09-7.92(5H, m), 7.77(1H, s), 7.65(2H, d, J=8.4Hz), 7.59-7.51(3H, m), 7.43(2H, d, J=8.4Hz), 7.17(2H, d, J=8.7Hz), 5.10(2H, s), 4.30(1H, m), 2.40-2.15(2H, m), 2.10-1.75(4H, m), 1.75-1.55(1H, m), 1.55-1.10(3H, m). Purity >90% (NMR) MS 580(M + 1)

[1915] 56 TABLE 56 Example No. 196 1H NMR(&dgr;) ppm 260 300MHz, DMSO-d6 8.22(1H, s), 7.95(1H, d, J=8.4Hz), 7.86(1H, d, J=8.4Hz), 7.69 and 7.18(4H, ABq, J=8.7Hz), 7.34(1H, t, J=8.0Hz), 6.80-6.69(3H, m), 4.83(2H, s), 4.31(1H, m), 2.98(3H, s), 2.84(3H, s), 2.29(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m) Purity >90% (NMR) MS 514(M + 1) Example No. 197 1H NMR(&dgr;) ppm 261 300MHz, DMSO-d6 8.23(1H, s), 7.95(1H, d, J=8.4Hz), 7.86(1H, d, J=8.7Hz), 7.69 and 7.18(4H, ABq, J=8.7Hz), 7.35(1H, t, J=8.4Hz), 6.80-6.70(3H, m), 4.82(2H, s), 4.31(1H, m), 3.40(4H, m), 2.29(2H, m), 2.00-1.75(4H, m), 1.70-1.15(10H, m) Purity >90% (NMR) MS 554(M + 1) Example No. 198 1H NMR(&dgr;) ppm 262 300MHz, DMSO-d6 12.75(1H, s), 8.23(1H, d, J=4.4Hz), 7.95 and 7.86(2H, ABq, J=8.6Hz), 7.69 and 7.19(4H, A′ B′ q, J=8.6Hz), 7.36(1H, t, # J=7.8Hz), 6.82(1H, d, J=9.3Hz), 6.73(1H, s), 6.71(1H, d, J=7.2Hz), 4.30(1H, brt, J=12.2Hz), 3.89(2H, d, J=6.0Hz), 3.59(2H, d, J=11.7Hz), 2.85(3H, s), 2.73(2H, t, J=10.5Hz), 2.41-2.20(2H, m), 1.98-1.59(8H, m), 1.46-1.18(5H, m) Purity >90% (NMR) MS 604(M + 1)

[1916] 57 TABLE 57 Example No. 199 1H NMR(&dgr;) ppm 263 300MHz, DMSO-d6 8.33(1H, s), 8.30(1H, d, J=8.9Hz), 8.06(1H, d, J=8.7Hz), 7.79(2H, d, J=8.7Hz), 7.70(2H, # d, J=8.7Hz), 7.61(2H, d, J=8.7Hz), 7.39(2H, d, J=8.8Hz), 5.28(2H, s), 4.39(1H, m), 2.50-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 542(M + 1) Example No. 200 1H NMR(&dgr;) ppm 264 (DMSO-d6) &dgr;: 8.23(1H, s), 7.96(1H, d, J=8.6Hz), 7.86(1H, d, J=8.6Hz), # 7.69(2H, d, J=8.4Hz), 7.52(1H, s), 7.50-7.30(4H, m), 7.18(2H, d, J=8.4Hz), 6.90(1H, d, J=8.3Hz), 6.84(1H, s), 6.74(1H, d, J=8.3Hz), 5.15(2H, s), 4.39-4.21(1H, m), 2.39-2.18(2H, m), 1.99-1.80(4H, m), 1.71-1.59(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 553(M + 1) Example No. 201 1H NMR(&dgr;) ppm 265 (DMSO-d6) &dgr;: 8.26(1H, s), 8.06(1H, d, J=8.7Hz), 7.92(1H, d, J=8.7Hz), 7.72(2H, d, J=8.7Hz), 7.47(4H, s), 7.38(1H, t, # J=8.2Hz), 7.20(2H, d, J=8.7Hz), 6.90(1H, d, J=8.2Hz), 6.83(1H, s), 6.74(1H, d, J=8.2Hz), 5.14(2H, s), 2.40-2.19(2H, m), 2.04-1.78(4H, m), 1.71-1.60(1H, m), 1.50-1.21(3H, m) Purity >90% (NMR) MS 553(M + 1)

[1917] 58 TABLE 58 Example No. 202 1H NMR(&dgr;) ppm 266 (DMSO-d6) &dgr;: 12.81(1H, brs), 8.24(1H, s), 7.99(1H, d, J=8.7Hz), 7.87(1H, d, J=8.7Hz), 7.69(2H, d, J=8.6Hz), 7.53-7.47(2H, m), 7.38(1H, t, J=8.2Hz), 7.26-7.16(4H, m), 6.89(1H, # d, J=8.2Hz), 6.82(1H, s), 6.73(1H, d, J=8.2Hz), 5.11(2H, s), 4.40-4.21(1H, m), 2.40-2.17(2H, m), 2.01-1.77(4H, m), 1.71-1.59(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 537(M + 1) Example No. 203 1H NMR(&dgr;) ppm 267 300MHz, DMSO-d6 12.74(1H, brs), 8.21(1H, s), 8.08(2H, d, J=9.0Hz), 7.93(1H, d, J=8.7Hz), 7.85(2h, d, J=8.7Hz), 7.58(2H, d, J=8.7Hz), 7.13(2H, d, J=8.7Hz), 6.83(2H, d, J=9.0Hz), 4.50-4.08(4H, m), 3.68-3.30(2H, m), 2.40-1.23(14H, m) Purity >90% (NMR) MS 541(M + 1) Example No. 204 1H NMR(&dgr;) ppm 268 300MHz, DMSO-d6 8.39-8.28(2H, m), 8.08(1H, d, J=8.8Hz), 7.76(2H, d, J=8.7Hz), 7.29(2H, d, J=8.7Hz), 7.25-7.13(2H, m), 6.80-6.60(3H, m), 4.46-3.98(4H, m), 3.51-3.42(1H, m), 3.20-3.04(1H, m), 2.39-1.20(14H, m) Purity >90% (NMR) MS

[1918] 59 TABLE 59 Example No. 205 1H NMR(&dgr;) ppm 269 300MHz, DMSO-d6 9.59(1H, brs), 8.23(1H, s), 8.04(1H, d, J=8.4Hz), 7.90(1H, d, J=8.4Hz), 7.62(2H, d, J=8.7Hz), 7.39(2H, 2H, # d, J=8.7Hz) 7.18(2H, d, J=8.7Hz), 6.63(2H, d, J=8.7Hz), 3.95-3.37(4H, m), 3.51-3.40(1H, m), 3.17-3.02(1H, m), 2.39-1.18(17H, m) Purity >90% (NMR) MS 553(M + 1) Example No. 206 1H NMR(&dgr;) ppm 270 300MHz, DMSO-d6 13.1(1H, brs), 8.33(1H, s), 8.29(1H, d, J=8.8Hz), # 8.06(1H, d, J=8.7Hz), 7.77(2H, d, J=8.7Hz), 7.59-7.52(4H, m), 7.35(2H, d, J=8.8Hz), 5.19(2H, s), 4.39(1H, m), 2.71(3H, s), 2.45-2.20(2H, m), 2.20-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 558(M + 1) Example No. 207 1H NMR(&dgr;) ppm 271 300MHz, DMSO-d6 8.29(1H, s), 8.26(1H, d, J=8.8Hz), 8.04(1H, d, J=8.7Hz), 7.73(2H, d, J=8.8Hz), 7.50-7.41(6H, m), 7.36(2H, # d, J=8.8Hz), 7.18-7.13(2H, m), 6.84(1H, s), 4.33(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 539(M + 1)

[1919] 60 TABLE 60 Example No. 208 1H NMR(&dgr;) ppm 272 300MHz, DMSO-d6 8.32(1H, s), 8.27(1H, d, J=9.0Hz), 8.07-8.00(3H, m), 7.79-7.70(3H, m), 7.51(2H, d, # J=8.1Hz), 7.40(2H, d, J=8.4Hz), 7.18(2H, d, J=8.7Hz), 4.99(2H, s), 4.34(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m). Purity >90% (NMR) MS 582(M + 1) Example No. 209 1H NMR(&dgr;) ppm 273 300MHz, DMSO-d6 8.24(1H, d, J=4.4Hz), 7.98 and 7.88(2H, ABq, J=8.6Hz), 7.70 and 7.19(4H, A′ B′ q, # J=8.4Hz), 7.35(1H, t, J=8.4Hz), 6.86(1H, d, J=8.1Hz), 6.79(1H, s), 6.71(1H, d, J=8.1Hz), 4.65-4.53(1H, m), 4.31(1H, brt, J=12.2Hz), 3.88-3.78(2H, m), 3.48(2H, t, J=9.0Hz), 2.39-2.19(2H, m), 1.02-1.71(6H, m), 1.70-1.50(3H, m), 1.46-1.19(3H, m) Purity >90% (NMR) MS 513(M + 1) Example No. 210 1H NMR(&dgr;) ppm 274 300MHz, DMSO-d6 12.75(1H, s), 8.23(1H, s), 7.96 and 7.87(2H, ABq, J=8.7Hz), 7.84-7.66(6H, m), 7.38(1H, t, # J=8.4Hz), 7.18(2H, d, J=8.4Hz), 6.91(1H, d, J=9.0Hz), 6.84(1H, s), 6.74(1H, d, J=8.1Hz), 5.26(2H, s), 4.31(1H, brt, J=12.2Hz), 2.40-2.20(2H, m), 1.99-1.76(4H, m), 1.69-1.58(1H, m), 1.45-1.20(3H, m) Purity >90% (NMR) MS 587(M + 1)

[1920] 61 TABLE 61 Example No. 211 1H NMR (&dgr;) ppm 275 300 MHz, DMSO-d6 8.29 (1H, s), 8.15 and 7.47 (2H, ABq, J=9.0 Hz), 7.77 and 7.24 (4H, ABq, J=8.9 Hz), 7.39 (1H, t, J=7.8 Hz), 6.84 (1H, d, J=9.3 Hz), 6.76 (1H, s), 6.75 (1H, d, J=9.5 Hz), 4.36 (1H, brt, J=12.2 Hz), 3.89 (2H, d, J=6.0 Hz), 3.42 (2H, d, J=10.8 Hz), 3.04-2.88 (2H, m), 2.78-2.60 (1H, m), 2.71 (2H, d, J=4.8 Hz), 2.38-2.20 (2H, m), Purity >90% (NMR) 2.07-1.80 (7H, m), 1.70-1.20 MS 540 (M + 1) (5H, m) Example No. 212 1H NMR (&dgr;) ppm 276 300 MHz, DMSO-d6 8.22 (1H, s), 7.93 and 7.87 (2H, ABq, J=8.6 Hz), 7.68 and 7.17 (4H, A′ B′ q, J=8.7 Hz), 7.43-7.33 (5H, m), 6.87 (1H, d, J=8.1 Hz), 7.18 (2H, d, J=8.4 Hz), 6.91 (1H, d, J=9.0 Hz), 6.81 (1H, s), 6.72 (1H, d, J=8.0 Hz), 5.08 (2H, s), 4.36 (1H, brt, J=12.2 Hz), 2.37-2.20 (2H, m), 1.98-1.78 (4H, m), 1.69-1.60 (1H, m), 1.41-1.21 (3H, m), 1.28 (9H, s) Purity >90% (NMR) MS 575 (M + 1) Example No. 213 1H NMR (&dgr;) ppm 277 300 MHz, DMSO-d6 8.23 (1H, s), 7.95 and 7.86 (2H, ABq, J=8.4 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.7 Hz), 7.62-7.36 (5H, m), 6.90 (1H, d, J=8.1 Hz), 6.84 (1H, s), 6.76 (1H, d, J=8.1 Hz), 5.19 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 2.40-2.19 (2H, m), 1.99-1.76 (4H, m), 1.68-1.55 (1H, m), 1.50-1.18 (3H, m) Purity >90% (NMR) MS 553 (M + 1)

[1921] 62 TABLE 62 Example No. 214 1H NMR (&dgr;) ppm 278 300 MHz, DMSO-d6 8.94 (1H, d, J=2.1 Hz), 8.60 (1H, dd, J=4.8, 1.5 Hz), 8.23 (1H, d, J=1.5 Hz), 8.12(1H, dt, J=8.1, 2.1 Hz), 7.93 (1H, d, J=8.7 Hz), 7.87 (1H, dd, J=8.7, 1.5 Hz), 7.70 (1H, d, J=8.7 Hz), 7.67-7.54 (3H, m), 7.50 (1H, dd, J=8.1, 4.8 Hz), 7.25 (2H, d, J=8.7 Hz), 7.21 (1H, m), 4.31 (1H, m), 2.38-2.19 (2H, m), 2.00-1.78 (4H, m), 1.65 (1H, m), 1.48-1.22 (3H, m). Purity >90% (NMR) MS 490 (M + 1) Example No. 215 1H NMR (&dgr;) ppm 279 300 MHz, DMSO-d6 12.75 (1H, brs), 8.23 (1H, s), 7.95 (1H, d, J=8.7 Hz), 7.86 (1H, d, J=8.7 Hz), 7.73 (2H, d, J=8.4 Hz), 7.71 (2H, d, J=8.4 Hz), 7.63-7.39 (2H, m), 7.52 (2H, d, J=8.4 Hz), 7.24 (2H, d, J=8.4 Hz), 7.18 (1H, m), 4.31 (1H, m), 2.39-2.20 (2H, m), 2.00-1.76 (4H, m), 1.65 (1H, m), 1.49-1.18 (3H, m). Purity >90% (NMR) MS 523 (M + 1) Example No. 216 1H NMR (&dgr;) ppm 280 300 MHz, DMSO-d6 12.77 (1H, s), 8.23 (1H, d, J=1.4 Hz), 7.95 (1H, d, J=8.6 Hz), 7.86 (1H, dd, J=8.6, 1.4 Hz), 7.70 (2H, d, J=8.7 Hz), 7.64 (2H, d, J=8.8 Hz), 7.56-7.48 (2H, m), 7.40 (1H, s), 7.23 (2H, d, J=8.7 Hz), 7.10 (1H, m), 7.03 (2H, d, J=8.8 Hz), 4.31 (1H, m), 3.80 (3H, s), 2.48-2.20 (2H, m), 2.00-1.88 (4H, m), 1.66 (1H, m), 1.50-1.21 (3H, m). Purity >90% (NMR) MS 519 (M + 1)

[1922] 63 TABLE 63 Example No. 217 1H NMR (&dgr;) ppm 281 (DMSO-d6) &dgr;: 12.80 (1H, brs), 8.23 (1H, s), 8.04 (1H, d, J=8.6 Hz), 7.96 (3H, d, J=8.6 Hz), 7.86 (1H, d, J =8.7 Hz), 7.63 (2H, d, J=8.6 Hz), 7.25 (2H, d, J=8.6 Hz), 5.50 (2H, s), 4.36-4.21 (1H, m), 3.27 (3H, s), 2.74 (3H, s), 2.40-2.19 (2H, m), 1.99-1.79 (4H, m), 1.71-1.60 (1H, m), 1.49-1.19 (3H, m) Purity >90% (NMR) MS 602 (M + 1) Example No. 218 1H NMR (&dgr;) ppm 282 300 MHz, DMSO-d6 12.9 (1H, brs), 8.25 (1H, s), 8.04 (1H, d, J=8.7 Hz), 7.91 (1H, d, J=8.6 Hz), 7.72 (2H, d, J=8.5 Hz), 7.67 (2H, d, J=8.7 Hz), 7.56 (2H, d, J=8.5 Hz), 7.26 (2H, d, J=8.7 Hz), 5.45 (2H, s), 4.31 (1H, m), 2.71 (3H, s), 2.40-2.15 (2H, m), 2.05-1.80 (4H, m), 1.75-1.55 (1H, m), 1.55-1.15 (3H, m). Purity >90% (NMR) MS 558 (M + 1) Example No. 219 1H NMR (&dgr;) ppm 283 300 MHz, DMSO-d6 8.21 (1H, d, J=1.5 Hz), 7.93 (1H, d, J=9.0 Hz), 7.84 (1H, dd, J=9.0, 1.5 Hz), 7.56 (2H, d, J=8.7 Hz), 7.42-7.30 (4H, m), 7.12 (2H, d, J=8.7 Hz), 4.53 (1H, brs), 4.36-4.20 (1H, m), 3.55 (2H, brs), 3.00-2.90 (1H, m), 2.70-2.58 (1H, m), 2.40-1.10 (18H, m) Purity >90% (NMR) MS 544 (M + 1)

[1923] 64 TABLE 64 Example No. 220 1H NMR (&dgr;) ppm 284 300 MHz, DMSO-d6 12.76 (1H, s), 8.23 (1H, s), 7.96 and 7.87 (2H, ABq, J=8.9 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.6 Hz), 7.55 (1H, s), 7.37 (1H, t, J=8.1 Hz), 6.91 (1H, d, J=7.8 Hz), 6.85 (1H, s), 6.74 (1H, d, J=7.5 Hz), 5.13 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 2.65 (3H, s), 2.41-2.20 (2H, m), 2.00-1.74 (4H, m), 1.70-1.59 (1H, m), 1.58-1.20 (3H, m) Purity >90% (NMR) MS 540 (M + 1) Example No. 221 1H NMR (&dgr;) ppm 285 300 MHz, DMSO-d6 8.23 (1H, s), 7.96 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.18 (4H, A′ B′ q, J=8.7 Hz), 7.37 (1H, t, J=8.2 Hz), 6.87 (1H, d, J=8.2 Hz), 6.82 (1H, s), 6.75 (1H, d, J=8.0 Hz), 5.24 (2H, s), 4.32 (1H, brt, J=12.2 Hz), 2.58 (3H, s), 2.38-2.20 (2H, m), 2.30 (3H, s), 2.00-1.79 (4H, m), 1.70-1.59 (1H, m), 1.44-1.20 (3H, m) Purity >90% (NMR) MS 554 (M + 1) Example No. 222 1H NMR (&dgr;) ppm 286 300 MHz, DMSO-d6 12.88 (1H, brs), 8.25 (s, 1H), 8.07-7.57 (11H, m), 7.26 (2H, d, J=8.7 Hz), 7.24 (1H, m), 4.34 (1H, m), 2.30-2.20 (2H, m), 2.03-1.78 (4H, m), 1.64 (1H, m), 1.49-1.19 (3H, m). Purity >90% (NMR) MS 557 (M + 1)

[1924] 65 TABLE 65 Example No. 223 1H NMR (&dgr;) ppm 287 300 MHz, DMSO-d6 10.96 (1H, brs), 8.21 (1H, d, J=1.4 Hz), 7.93 (1H, d, J=8.7 Hz), 7.84 (1H, dd, J=8.7, 1.4 Hz), 7.76-7.40 (7H, m), 7.18 (2H, d, J=8.0 Hz), 4.24-4.16 (2H, m), 2.40-1.12 (18H, m) Purity >90% (NMR) MS 544 (M + 1) Example No. 224 1H NMR (&dgr;) ppm 288 (DMSO-d6) &dgr;: 8.22 (1H, s), 8.07 (1H, d, J=8.4 Hz), 7.92 (1H, d, J=8.4 Hz), 7.54 (2H, d, J=8.7 Hz), 7.40 (2H, d, J=8.4 Hz), 7.30 (2H, d, J=8.4 Hz), 7.14 (2H, d, J=8.7 Hz), 4.61 (2H, s), 4.48-4.32 (1H, m), 3.82 (1H, brd, J=12.3 Hz), 3.65-3.47 (2H, m), 3.10 (brdd, J=8.4, 12.3 Hz), 2.40-2.20 (2H, m), 2.09-1.76 (6H, m), 1.71-1.16 (6H, m) Purity >90% (NMR) MS 544 (M + 1) Example No. 225 1H NMR (&dgr;) ppm 289 (DMSO-d6) &dgr;: 12.83 (1H, brs), 8.21(1H, s), 8.10 (1H, brs), 7.01-7.91 (2H, m), 7.89-7.82 (2H, m), 7.75 (1H, d, J=8.0 Hz), 7.59 (2H, d, J=8.7 Hz), 7.53 (4H, s), 7.46 (1H, brs), 7.12 (2H, d, J=8.7 Hz), 7.23 (2H, s), 4.35-4.17 (1H, m), 2.38-2.20 (2H, m), 1.99-1.79 (4H, m), 1.71-1.59 (1H, m), 1.48-1.18 (3H, m) Purity >90% (NMR) MS 580 (M + 1)

[1925] 66 TABLE 66 Example No. 226 1H NMR (&dgr;) ppm 290 300 MHz, DMSO-d6 8.33 and 8.08 (2H, ABq, J=8.7 Hz), 8.31 (1H, m), 7.66 and 7.26 (4H, A′ B′ q, J=9.2 Hz), 7.42 and 7.39 (4H, A″B″q, J=8.7 Hz), 4.57 (2H, s), 4.50 (1H, brt, J=12.2 Hz), 3.85-3.62 (3H, m), 3.28-3.16 (2H, m), 2.42-2.23 (2H, m), 2.14-1.81 (6H, m), 1.72-1.25 (6H, m) Purity >90% (NMR) MS 544 (M + 1) Example No. 227 1H NMR (&dgr;) ppm 291 300 MHz, DMSO-d6 8.43 (1H, d, J=5.0 Hz), 8.23 (1H, s), 7.96 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.18 (4H, A′ B′ q, J=8.6 Hz), 7.57 (1H, s), 7.47 (1H, d, J=5.0 Hz), 7.40 (2H, t, J=8.2 Hz), 6.91 (1H, d, J=8.3 Hz), 6.85 (1H, s), 6.77 (1H, d, J=7.9 Hz), 5.25 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 2.40-2.19 (2H, m), 1.99-1.75 (4H, m), 1.73-1.57 (1H, m), 1.49-1.19 (3H, m) Purity >90% (NMR) MS 554 (M + 1) Example No. 228 1H NMR (&dgr;) ppm 292 300 MHz, DMSO-d6 12.80 (1H, brs), 8.22 (1H, s), 7.94 (1H, d, J=8.6 Hz), 7.87 (1H, d, J=8.6 Hz), 7.60 (2H, d, J=8.7 Hz), 7.32 (2H, d, J=8.7 Hz), 7.17 (2H, d, J=8.7 Hz), 6.70 (2H, d, J=8.7 Hz), 4.35-3.97 (4H, m), 3.62-3.11 (2H, m), 2.96 (6H, s), 2.39-1.12 (14H, m) Purity >90% (NMR) MS 567 (M + 1)

[1926] 67 TABLE 67 Example No. 229 1H NMR (&dgr;) ppm 293 300 MHz, DMSO-d6 8.25 (1H, s), 8.20 (1H, s), 8.04 (1H, dd, J=8.1, 1.8 Hz), 7.92 (1H, d, J=8.1 Hz), 7.84 (1H, d, J=9.9 Hz), 7.62-7.50 (7H, m), 7.12 (2H, d, J=8.7 Hz), 5.14 (2H, s), 4.36 (2H, q, J=6.9 Hz), 4.30-4.20 (1H, m), 2.38-2.18 (2H, m), 1.98-1.18 (8H, m), 1.35 (3H, t, J=6.9 Hz) Purity >90% (NMR) MS 608 (M + 1) Example No. 230 1H NMR (&dgr;) ppm 294 300 MHz, DMSO-d6 8.35 (1H, s), 8.27 (1H, d, J=8.7 Hz), 8.05 (1H, d, J=9.0 Hz), 7.87 (2H, d, J=8.7 Hz), 7.74 (1H, t, J=8.1 Hz), 7.64 (1H, d, J=7.8 Hz), 7.59-7.50 (2H, m), 7.36 (2H, d, J=8.7 Hz), 4.39 (1H, m), 2.40-2.15 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.20 (3H, m). Purity about 90% (NMR) MS 481 (M + 1) Example No. 231 1H NMR (&dgr;) ppm 295 300 MHz DMSO-d6 12.78 (1H, brs), 8.23 (1H, d, J=1.5 Hz), 7.96 (1H, d, J=8.7 Hz), 7.87(1H, dd, J=8.7, 1.5 Hz), 7.75 (2H, d, J=8.4 Hz), 7.63 (2H, d, J=8.4 Hz), 7.52 (2H, d, J=8.4 Hz), 7.24 (2H, d, J=8.4 Hz), 5.47 (2H, s), 4.29 (1H, m), 2.97 (6H, brs), 2.72 (3H, s), 2.39-2.16 (2H, m), 2.00-1.78 (4H, m), 1.71-1.59 (1H, m), 1.49-1.17 (3H, m). Purity about 90% (NMR) MS 595 (M + 1)

[1927] 68 TABLE 68 Example No. 232 1H NMR (&dgr;) ppm 296 300 MHz, DMSO-d6 12.8 (1H, brs), 8.22 (1H, s), 7.96 (1H, d, J=8.7 Hz), 7.86 (1H, d, J=8.6 Hz), 7.70 (1H, s), 7.59 (2H, d, J=8.7 Hz), 7.53-7.50 (5H, m), 7.42 (1H, d, J=7.9 Hz), 7.12 (2H, d, J=8.7 Hz), 5.11 (2H, s), 4.27 (1H, m), 3.01 (3H, brs), 2.97 (3H, brs), 2.40-2.15 (2H, m), 2.00-1.75 (4H, m), 1.75-1.55 (1H, m), 1.50-1.15 (3H, m). Purity >90% (NMR) MS 608 (M + 1) Example No. 233 1H NMR (&dgr;) ppm 297 DMSO-d6 13.20 (1H, brs), 8.99 (1H, s), 8.32 (1H, s), 8.25 (1H, d, J=8.8 Hz), 8.04 (1H, d, J=8.6 Hz), 7.79-7.74 (4H, m), 7.60 (2H, d, J=8.5 Hz), 7.30 (2H, d, J=8.7 Hz), 5.26 (2H, s), 4.36 (1H, m), 2.72 (3H, s), 2.50-2.15 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.15 (3H, m) Purity >90% (NMR) MS 553 (M + 1 − HCl) Example No. 234 1H NMR (&dgr;) ppm 298 DMSO-d6 8.77 (1H, d, J=3.6 Hz), 8.36-8.26 (3H, m), 8.08 (1H, d, J=8.8 Hz), 7.79 (2H, d, J=8.7 Hz), 7.72-7.64 (3H, m), 7.58 (2H, d, J=8.4 Hz), 7.30 (2H, d, J=8.7 Hz), 5.26 (2H, s), 4.38 (1H, m), 2.50-2.15 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.15 (3H, m). Purity >90% (NMR) MS 538 (M + 1 − 2HCl)

[1928] 69 TABLE 69 Example No. 235 1H NMR (&dgr;) ppm 299 300 MHz, DMSO-d6 12.74 (1H, brs), 8.67 (1H, dd, J=3.1, 1.6 Hz), 8.21 (1H, d, J=1.6 Hz), 7.93 (1H, dJ=8.6 Hz), 7.90-7.80 (2H, m), 7.60-7.50 (7H, m), 7.09 (2H, d, J=8.7 Hz), 5.16 (2H, s), 4.26 (1H, m), 2.40-2.20 (2H, m), 2.00-1.60 (5H, m), 1.50-1.20 (3H, m) Purity >90% (NMR) MS APCI-Ms 538 (M + 1) Example No. 236 1H NMR (&dgr;) ppm 300 300 MHz, DMSO-d-6 8.40-7.40 (11H, m), 2.95, 2.81 (3H, each d, J=4.7 Hz), 2.40-2.20 (2H, m), 2.10-1.80 (4H, m), 1.70-1.60 (1H, m), 1.50-1.20 (3H, m) Purity >90% (NMR) MS APCI-Ms 555 (M + 1) Example No. 237 1H NMR (&dgr;) ppm 301 300 MHz, DMSO-d6 8.21 (1H, s), 8.15 (1H, d, J=9.5 Hz), 8.02 (1H, s), 8.00-7.80 (3H, m), 7.70-7.50 (6H, m), 7.12 (2H, d, J=8.7 Hz), 5.16 (2H, s), 4.28 (1H, m), 2.40-2.20 (2H, m), 2.00-1.80 (4H, m), 1.65 (1H, m), 1.50-1.20 (3H, m) Purity >90% (NMR) MS FAB-Ms 605 (M + 1)

[1929] 70 TABLE 70 Example No. 238 1H NMR (&dgr;) ppm 302 300 MHz, DMSO-d6 12.80 (1H, brs), 8.54 (1H, s), 8.25 (1H, s), 7.98 and 7.88 (2H, Abq, J=8.6 Hz), 7.76 (2H, d, J=8.6 Hz), 7.53-7.31 (3H, m), 6.61 (1H, s), 5.46 (2H, s), 4.32 (1H, brt), 2.40-2.20 (2H, m), 2.02-1.79 (4H, m), 1.69-1.59 (1H, m), 1.48-1.19 (3H, m) Purity >90% (NMR) MS APCI-Ms 521 (M + 1) Example No. 239 1H NMR (&dgr;) ppm 303 300 MHz, DMSO-d6 12.79 (1H, brs), 8.60 (2H, d, J=1.5 Hz), 8.53 (1H, s), 8.25 (1H, s), 7.98 and 7.85 (2H, ABq, J=9.4 Hz), 7.76 (2H, d, J=9.0 Hz), 7.44 (4H, d, J=6.5 Hz), 6.69 (1H, s), 5.53 (2H, s), 4.32 (1H, brt), 2.40-2.19 (2H, m), 2.03-1.82 (4H, m), 1.72-1.61 (1H, m), 1.42-1.22 (3H, m) Purity >90% (NMR) MS APCI-Ms 522 (M + 1) Example No. 240 1H NMR (&dgr;) ppm 304 300 MHz, DMSO-d6 8.90 (1H, s), 8.32 (1H, s), 8.28 (1H, s), 8.25 (1H, d, J=8.3 Hz), 8.05 (1H, d, J=8.8 Hz), 7.96 (1H, s), 7.93 (1H, d, J=8.8 Hz), 7.83 (1H, d, J=8.4 Hz), 7.68-7.59 (2H, m), 7.54 (2H, d, J=8.8 Hz), 4.37 (1H, brt), 2.30 (2H, m), 2.00 (2H, m), 1.88 (2H, m), 1.67 (1H, m), 1.5-1.2 (3H, m) Purity >90% (NMR) MS APCI-Ms 525 (M + 1)

[1930] 71 TABLE 71 Ex. No. Formula MS 1001 305 364 (M + H) 1002 306 454 (M + H) 1003 307 398 (M + H) 1004 308 357 (M + H) 1005 309 322 (M + H) 1006 310 385 (M + H)

[1931] 72 TABLE 72 Ex. No. Formula MS 1007 311 357 (M + H) 1008 312 416 (M + H) 1009 313 310 (M + H) 1010 314 390 (M + H) 1011 315 395 (M + H) 1012 316 366 (M + H)

[1932] 73 TABLE 73 Ex. No. Formula MS 1013 317 374 (M + H) 1014 318 382 (M + H) 1015 319 350 (M + H) 1016 320 402 (M + H) 1017 321 414 (M + H) 1018 322 340 (M + H)

[1933] 74 TABLE 74 Ex. No. Formula MS 1019 323 350 (M + H) 1020 324 380 (M + H) 1021 325 366 (M + H) 1022 326 378 (M + H) 1023 327 402 (M + H)

[1934] 75 TABLE 75 Ex. No. Formula MS 1024 328 518 (M + H) 1025 329 408 (M + H) 1026 330 336 (M + H) 1027 331 408 (M + H) 1028 332 366 (M + H) 1029 333 362 (M + H)

[1935] 76 TABLE 76 Ex. No. Formula MS 1030 334 473 (M + H) 1031 335 338 (M + H) 1032 336 307 (M + H) 1033 337 406 (M + H) 1034 338 466 (M + H) 1035 339 412 (M + H)

[1936] 77 TABLE 77 Ex. No. Formula MS 1036 340 412 (M + H) 1037 341 428 (M + H) 1038 342 466 (M + H) 1039 343 406 (M + H) 1040 344 417 (M + H) 1041 345 440 (M + H)

[1937] 78 TABLE 78 Ex. No. Formula MS 1042 346 417 (M + H) 1043 347 440 (M + H) 1044 348 312 (M + H) 1045 349 423 (M + H) 1046 350 352 (M + H) 1047 351 307 (M + H)

[1938] 79 TABLE 79 Ex. No. Formula MS 1048 352 374(M + H) 1049 353 398 (M + H) 1050 354 326 (M + H) 1051 355 442 (M + H) 1052 356 518 (M + H)

[1939] 80 TABLE 80 Ex. No. Formula MS 1053 357 442 (M + H) 1054 358 376 (M + H) 1055 359 442 (M + H) 1056 360 352 (M + H) 1057 361 367 (M + H) 1058 362 367 (M + H)

[1940] 81 TABLE 81 Ex. No. Formula MS 1059 363 364 (M + H) 1060 364 324 (M + H) 1061 365 352 (M + H) 1062 366 357 (M + H) 1063 367 360 (M + H) 1064 368 351 (M + H)

[1941] 82 TABLE 82 Ex. No. Formula MS 1065 369 351 (M + H) 1066 370 366 (M + H) 1067 371 367 (M + H) 1068 372 364 (M + H) 1069 373 350 (M + H) 1070 374 306 (M + H)

[1942] 83 TABLE 83 Ex. No. Formula MS 1071 375 365 (M + H) 1072 376 455 (M + H) 1073 377 399 (M + H) 1074 378 358 (M + H) 1075 379 337 (M + H) 1076 380 386 (M + H)

[1943] 84 TABLE 84 Ex. No. Formula MS 1077 381 358 (M + H) 1078 382 417 (M + H) 1079 383 311 (M + H) 1080 384 391 (M + H) 1081 385 396 (M + H) 1082 386 367 (M + H)

[1944] 85 TABLE 85 Ex. No. Formula MS 1083 387 375 (M + H) 1084 388 351 (M + H) 1085 389 383 (M + H) 1086 390 403 (M + H) 1087 391 415 (M + H) 1088 392 341 (M + H)

[1945] 86 TABLE 86 Ex. No. Formula MS 1089 393 351 (M + H) 1090 394 381 (M + H) 1091 395 367 (M + H) 1092 396 379 (M + H) 1093 397 403 (M + H)

[1946] 87 TABLE 87 Ex. No. Formula MS 1094 398 519 (M + H) 1095 399 409 (M + H) 1096 400 337 (M + H) 1097 401 409 (M + H) 1098 402 367 (M + H) 1099 403 363 (M + H)

[1947] 88 TABLE 88 Ex. No. Formula MS 1100 404 474 (M + H) 1101 405 339 (M + H) 1102 406 308 (M + H) 1103 407 467 (M + H) 1104 408 413 (M + H) 1105 409 413 (M + H)

[1948] 89 TABLE 89 Ex. No. Formula MS 1106 410 429 (M + H) 1107 411 467 (M + H) 1108 412 1109 413 1110 414 441 (M + H) 1111 415 418 (M + H)

[1949] 90 TABLE 90 Ex. No. Formula MS 1112 416 313 (M + H) 1113 417 308 (M + H) 1114 418 375 (M + H) 1115 419 399 (M + H) 1116 420 327 (M + H) 1117 421 443 (M + H)

[1950] 91 TABLE 91 Ex. No. Formula MS 1118 422 519 (M + H) 1119 423 443 (M + H) 1120 424 377 (M + H) 1121 425 443 (M + H) 1122 426 353 (M + H)

[1951] 92 TABLE 92 Ex. No. Formula MS 1123 427 368 (M + H) 1124 428 368 (M + H) 1125 429 365 (M + H) 1126 430 325 (M + H) 1127 431 353 (M + H) 1128 432 358 (M + H)

[1952] 93 TABLE 93 Ex. No. Formula MS 1129 361 (M + H) 1130 352 (M + H) 1131 352 (M + H) 1132 367 (M + H) 1133 368 (M + H) 1134 365 (M + H)

[1953] 94 TABLE 94 Ex. No. Formula MS 1135 433 351 (M + H) 1136 434 307 (M + H) 1137 435 385 (M + H) 1138 436 365 (M + H) 1139 437 467 (M + H) 1140 438 387 (M + H)

[1954] 95 TABLE 95 Ex. No. Formula MS 1141 439 322 (M + H) 1142 440 364 (M + H) 1143 441 323 (M + H) 1144 442 363 (M + H) 1145 443 484 (M + H) 1146 444 385 (M + H)

[1955] 96 TABLE 96 Ex. No. Formula MS 1147 445 427 (M + H) 1148 446 420 (M + H) 1149 447 508 (M + H) 1150 448 458 (M + H) 1151 449 458 (M + H)

[1956] 97 TABLE 97 Ex. No. Formula MS 1152 450 474 (M + H) 1153 451 458 (M + H) 1154 452 508 (M + H) 1155 453 454 (M + H)

[1957] 98 TABLE 98 Ex. No. Formula MS 1156 454 470 (M + H) 1157 455 496 (M + H) 1158 456 482 (M + H) 1159 457 448 (M + H) 1160 458 488 (M + H)

[1958] 99 TABLE 99 Ex. No. Formula MS 1161 459 468 (M + H) 1162 460 447 (M + H) 1163 461 466 (M + H) 1164 462 526 (M + H) 1165 463 420 (M + H)

[1959] 100 TABLE 100 Ex. No. Formula MS 1166 464 490 (M + H) 1167 465 435 (M + H) 1168 466 436 (M + H) 1169 467 436 (M + H) 1170 468 404 (M + H) 1171 469 406 (M + H)

[1960] 101 TABLE 101 Ex. No. Formula MS 1172 470 392 (M + H) 1173 471 420 (M + H) 1174 472 406 (M + H) 1175 473 420 (M + H) 1176 474 523 (M + H) 1177 475 406 (M + H)

[1961] 102 TABLE 102 Ex. No. Formula MS 1178 476 447 (M + H) 1179 477 433 (M + H) 1180 478 509 (M + H) 1181 479 513 (M + H)

[1962] 103 TABLE 103 Ex. No. Formula MS 1182 480 497 (M + H) 1183 481 496 (M + H) 1184 482 418 (M + H) 1185 483 508 (M + H) 1186 484 490 (M + H)

[1963] 104 TABLE 104 Ex. No. Formula MS 1187 485 441 (M + H) 1188 486 455 (M + H) 1189 487 455 (M + H) 1190 488 513 (M + H) 1191 489 504 (M + H) 1192 490 494 (M + H)

[1964] 105 TABLE 105 Ex. No. Formula MS 1193 491 512 (M + H) 1194 492 504 (M + H) 1195 493 516 (M + H) 1196 494 497 (M + H) 1197 495 456 (M + H) 1198 496 509 (M + H)

[1965] 106 TABLE 106 Ex. No. Formula MS 1199 497 483(M + H) 1200 498 427(M + H) 1201 499 427(M + H) 1202 500 477(M + H) 1203 501 519(M + H) 1204 502 440(M + H)

[1966] 107 TABLE 107 Ex. No. Formula MS 1205 503 454(M + H) 1206 504 325(M + H) 1207 505 341(M + H) 1208 506 385(M + H) 1209 507 363(M + H) 1210 508 332(M + H)

[1967] 108 TABLE 108 Ex. No. Formula MS 1211 509 351(M + H) 1212 510 335(M + H) 1213 511 349(M + H) 1214 512 321(M + H) 1215 513 375(M + H) 1216 514 367(M + H)

[1968] 109 TABLE 109 Ex. No. Formula MS 1217 515 433(M + H) 1218 516 391(M + H) 1219 517 337(M + H) 1220 518 385(M + H) 1221 519 341(M + H) 1222 520 332(M + H)

[1969] 110 TABLE 110 Ex. No. Formula MS 1223 521 395(M + H) 1224 522 375(M + H) 1225 523 351(M + H) 1226 524 321(M + H) 1227 525 426(M + H) 1228 526 460(M + H)

[1970] 111 TABLE 111 Ex. No. Formula MS 1229 527 442(M + H) 1230 528 468(M + H) 1231 529 456(M + H) 1232 530 494(M + H) 1233 531 451(M + H) 1234 532 468(M + H)

[1971] 112 TABLE 112 Ex. No. Formula MS 1235 533 498(M + H) 1236 534 476(M + H) 1237 535 502(M + H) 1238 536 505(M + H) 1239 537 469(M + H)

[1972] 113 TABLE 113 Ex. No. Formula MS 1240 538 483(M + H) 1241 539 408(M + H) 1242 540 460(M + H) 1243 541 468(M + H) 1244 542 494(M + H) 1245 543 454(M + H)

[1973] 114 TABLE 114 Ex. No. Formula MS 1246 544 468(M + H) 1247 545 498(M + H) 1248 546 482(M + H) 1249 547 468(M + H) 1250 548 460(M + H)

[1974] 115 TABLE 115 Ex. No. Formula MS 1251 549 442(M + H) 1252 550 468(M + H) 1253 551 456(M + H) 1254 552 494(M + H)

[1975] 116 TABLE 116 Ex. No. Formula MS 1255 553 451(M + H) 1256 554 468(M + H) 1257 555 498(M + H) 1258 556 470(M + H)

[1976] 117 TABLE 117 Ex. No. Formula MS 1259 557 476(M + H) 1260 558 502(M + H) 1261 559 505(M + H) 1262 560 469(M + H)

[1977] 118 TABLE 118 Ex. No. Formula MS 1263 561 483(M + H) 1264 562 408(M + H) 1265 563 460(M + H) 1266 564 468(M + H)

[1978] 119 TABLE 119 Ex. No. Formula MS 1267 565 494(M + H) 1268 566 454(M + H) 1269 567 468(M + H) 1270 568 498(M + H)

[1979] 120 TABLE 120 Ex. No. Formula MS 1271 569 482(M + H) 1272 570 468(M + H) 1273 571 494(M + H) 1274 572 484(M + H)

[1980] 121 TABLE 121 Ex. No. Formula MS 1275 573 519 (M + H) 1276 574 427 (M + H) 1277 575 456 (M + H) 1278 576 516 (M + H)

[1981] 122 TABLE 122 Ex. No. Formula MS 1279 577 436 (M + H) 1280 578 426 (M + H) 1281 579 440 (M + H) 1282 580 454 (M + H) 1283 581 468 (M + H)

[1982] 123 TABLE 123 Ex. No. Formula MS 1284 582 482 (M + H) 1285 583 406 (M + H) 1286 584 420 (M + H) 1287 585 508 (M + H) 1288 586 508 (M + H)

[1983] 124 TABLE 124 Ex. No. Formula MS 1289 587 509 (M + H) 1290 588 455 (M + H) 1291 589 494 (M + H) 1292 590 418 (M + H)

[1984] 125 TABLE 125 Ex. No. Formula MS 1293 591 490 (M + H) 1294 592 496 (M + H) 1295 593 477 (M + H) 1296 594 508 (M + H) 1297 595 470 (M + H)

[1985] 126 TABLE 126 Ex. No. Formula MS 1298 596 435 (M + H) 1299 597 488 (M + H) 1300 598 454 (M + H) 1301 599 504 (M + H)

[1986] 127 TABLE 127 Ex. No. Formula MS 1302 600 513 (M + H) 1303 601 399 (M + H) 1304 602 530 (M + H) 1305 603 504 (M + H) 1306 604 440 (M + H)

[1987] 128 TABLE 128 Ex. No. Formula MS 1307 605 494 (M + H) 1308 606 508 (M + H) 1309 607 518 (M + H) 1310 608 532 (M + H) 1311 609 522 (M + H)

[1988] 129 TABLE 129 Ex. No. Formula MS 1312 610 546 (M + H) 1313 611 484 (M + H) 1314 612 517 (M + H) 1315 613 488 (M + H) 1316 614 481 (M + H)

[1989] 130 TABLE 130 Ex. No. Formula MS 1317 615 413 (M + H) 1318 616 423 (M + H) 1319 617 504 (M + H) 1320 618 510 (M + H) 1321 619 522 (M + H) 1322 620 522 (M + H)

[1990] 131 TABLE 131 Ex. No. Formula MS 1323 621 484 (M + H) 1324 622 449 (M + H) 1325 623 502 (M + H) 1326 624 491 (M + H) 1327 625 496 (M + H)

[1991] 132 TABLE 132 Ex. No. Formula MS 1328 626 497 (M + H) 1329 627 470 (M + H) 1330 628 530 (M + H) 1331 629 502 (M + H) 1332 630 522 (M + H)

[1992] 133 TABLE 133 Ex. No. Formula MS 1333 631 491 (M + H) 1334 632 536 (M + H) 1335 633 547 (M + H) 1336 634 484 (M + H) 1337 635 484 (M + H) 1338 636 498 (M + H)

[1993] 134 TABLE 134 Ex. No. Formula MS 1339 637 528 (M + H) 1340 638 498 (M + H) 1341 639 514 (M + H) 1342 640 513 (M + H) 1343 641 488 (M + H) 1344 642 502 (M + H)

[1994] 135 TABLE 135 Ex. No. Formula MS 1345 643 488 (M + H) 1346 644 502 (M + H) 1347 645 499 (M + H) 1348 646 480 (M + H) 1349 647 522 (M + H) 1350 648 546 (M + H)

[1995] 136 TABLE 136 Ex. No. Formula MS 1351 649 482 (M + H) 1352 650 484 (M + H) 1353 651 609 (M + H) 1354 652 532 (M + H) 1355 653 480 (M + H) 1356 654 566 (M + H)

[1996] 137 TABLE 137 Ex. No. Formula MS 1357 655 602 (M + H) 1358 656 596 (M + H) 1359 657 491 (M + H) 1360 658 491 (M + H) 1361 659 491 (M + H) 1362 660 496 (M + H)

[1997] 138 TABLE 138 Ex. No. Formula MS 1363 661 512 (M + H) 1364 662 494 (M + H) 1365 663 488 (M + H) 1366 664 481 (M + H) 1367 665 524 (M + H) 1368 666 497 (M + H)

[1998] 139 TABLE 139 Ex. No. Formula MS 1369 667 472 (M + H) 1370 668 469 (M + H) 1371 669 470 (M + H) 1372 670 469 (M + H) 1373 671 494 (M + H) 1374 672 458 (M + H)

[1999] 140 TABLE 140 Ex. No. Formula MS 1375 673 612 (M + H) 1376 674 554 (M + H) 1377 675 542 (M + H) 1378 676 526 (M + H) 1379 677 496 (M + H) 1380 678 510 (M + H)

[2000] 141 TABLE 141 Ex. No. Formula MS 1381 679 540 (M + H) 1382 680 525 (M + H) 1383 681 558 (M + H) 1384 682 523 (M + H) 1385 683 539 (M+ H)

[2001] 142 TABLE 142 Ex. No. Formula MS 1386 684 533 (M + H) 1387 685 500 (M + H) 1388 686 485 (M + H) 1389 687 523 (M + H) 1390 688 512 (M + H)

[2002] 143 TABLE 143 Ex. No. Formula MS 1391 689 540 (M + H) 1392 690 527 (M + H) 1393 691 525 (M + H) 1394 692 507 (M + H) 1395 693 491 (M + H) 1396 694 506 (M + H)

[2003] 144 TABLE 144 Ex. No. Formula MS 1397 695 522 (M + H) 1398 696 538 (M + H) 1399 697 522 (M + H) 1400 698 530 (M + H) 1401 699 600 (M + H) 1402 700 504 (M + H)

[2004] 145 TABLE 145 Ex. No. Formula MS 1403 701 534 (M + H) 1404 702 475 (M +H) 1405 703 472 (M + H) 1406 704 455 (M + H) 1407 705 469 (M + H) 1408 706 547 (M + H)

[2005] 146 TABLE 146 Ex. No. Formula MS 1409 707 529 (M + H) 1410 708 435 (M + H) 1411 709 504 (M + H) 1412 710 469 (M + H) 1413 711 522 (M + H) 1414 712 488 (M + H)

[2006] 147 TABLE 147 Ex. No. Formula MS 1415 713 502 (M + H) 1416 714 488 (M + H) 1417 715 502 (M + H) 1418 716 455 (M + H) 1419 717 455 (M + H) 1420 718 522 (M + H)

[2007] 148 TABLE 148 Ex. No. Formula MS 1421 719 469 (M + H) 1422 720 536 (M + H) 1423 721 510 (M + H) 1424 722 494 (M + H) 1425 723 458 (M + H)

[2008] 149 TABLE 149 Ex. No. Formula MS 1426 724 612 (M + H) 1427 725 526 (M + H) 1428 726 480 (M + H) 1429 727 441 (M + H) 1430 728 511 (M + H)

[2009] 150 TABLE 150 Ex. No. Formula MS 1431 729 530 (M + H) 1432 730 497 (M + H) 1433 731 441 (M + H) 1434 732 491 (M + H) 1435 733 491 (M + H) 1436 734 491 (M + H)

[2010] 151 TABLE 151 Ex. No. Formula MS 1437 735 524 (M + H) 1438 736 508 (M + H) 1439 737 474 (M + H) 1440 738 490 (M + H) 1441 739 508 (M + H) 1442 740 474 (M + H)

[2011] 152 TABLE 152 Ex. No. Formula MS 1443 741 516 (M + H) 1444 742 600 (M + H) 1445 743 504 (M + H) 1446 744 534 (M + H) 1447 745 475 (M + H)

[2012] 153 TABLE 153 Ex. No. Formula MS 1448 746 530 (M + H) 1449 747 440 (M + H) 1450 748 490 (M + H) 1451 749 474 (M + H) 1452 750 441 (M + H) 1453 751 508 (M + H)

[2013] 154 TABLE 154 Ex. No. Formula MS 1454 752 455 (M + H) 1455 753 522 (M + H) 1456 754 496 (M + H) 1457 755 516 (M + H) 1458 756 426 (M + H) 1459 757 482 (M + H)

[2014] 155 TABLE 155 Ex. No. Formula MS 1460 758 486 (M + H) 1461 759 516 (M + H) 1462 760 427 (M + H) 1463 761 476 (M + H) 1464 762 460 (M + H) 1465 763 502 (M + H)

[2015] 156 TABLE 156 Ex. No. Formula MS 1466 764 586 (M + H) 1467 765 518 (M + H) 1468 766 530 (M + H) 1469 767 598 (M + H) 1470 768 512 (M + H) 1471 769 544 (M + H)

[2016] 157 TABLE 157 Ex. No. Formula MS 1472 770 440 (M + H) 1473 771 490 (M + H) 1474 772 474 (M + H) 1475 773 441 (M + H) 1476 774 508 (M + H) 1477 775 455 (M + H)

[2017] 158 TABLE 158 Ex. No. Formula MS 1478 776 522 (M + H) 1479 777 496 (M + H) 1480 778 516 (M + H) 1481 779 426 (M + H) 1482 780 482 (M + H)

[2018] 159 TABLE 159 Ex. No. Formula MS 1483 781 486 (M + H) 1484 782 516 (M + H) 1485 783 427 (M + H) 1486 784 476 (M + H)

[2019] 160 TABLE 160 Ex. No. Formula MS 1487 785 460 (M + H) 1488 786 502 (M + H) 1489 787 586 (M + H) 1490 788 518 (M + H)

[2020] 161 TABLE 161 Ex. No. Formula MS 1491 789 530 (M + H) 1492 790 598 (M + H) 1493 791 512 (M + H) 1494 792 544 (M + H)

[2021] 162 TABLE 162 Ex. No. Formula MS 1495 793 580 (M + H) 1496 794 550 (M + H) 1497 795 606 (M + H) 1498 796 580 (M + H) 1499 797 550 (M + H)

[2022] 163 TABLE 163 Ex. No. Formula MS 1500 798 606 (M + H) 1501 799 630 (M + H) 1502 800 600 (M + H) 1503 801 656 (M + H)

[2023] 164 TABLE 164 Ex. No. Formula MS 1504 802 630 (M + H) 1505 803 600 (M + H) 1506 804 656 (M + H) 1507 805 580 (M + H)

[2024] 165 TABLE 165 Ex. No. Formula MS 1508 806 550 (M + H) 1509 807 606 (M + H) 1510 808 580 (M + H) 1511 809 550 (M + H) 1512 810 546 (M + H)

[2025] 166 TABLE 166 Ex. No. Formula MS 1513 811 516 (M + H) 1514 812 572 (M + H) 1515 813 546 (M + H) 1516 814 516 (M + H) 1517 815 572 (M + H)

[2026] 167 TABLE 167 Ex. No. Formula MS 1518 816 602 (M + H) 1519 817 572 (M + H) 1520 818 628 (M + H) 1521 819 606 (M + H)

[2027] 168 TABLE 168 Ex. No. Formula MS 1522 820 573 (M + H) 1523 821 606 (M + H) 1524 822 602 (M + H) 1525 823 572 (M + H)

[2028] 169 TABLE 169 Ex. No. Formula MS 1526 824 628 (M + H) 1527 825 606 (M + H) 1528 826 606 (M + H) 1529 827 614 (M + H)

[2029] 170 TABLE 170 Ex. No. Formula MS 1530 828 584 (M + H) 1531 829 640 (M + H) 1532 830 618 (M + H) 1533 831 614 (M + H) 1534 832 584 (M + H)

[2030] 171 TABLE 171 Ex. No. Formula MS 1535 833 640 (M + H) 1536 834 627 (M + H) 1537 835 627 (M + H)

[2031] 172 TABLE 172 Ex. No. Formula MS 1538 836 560 (M + H) 1539 837 634 (M + H) 1540 838 593 (M + H) 1541 839 627 (M + H)

[2032] 173 TABLE 173 Ex. No. Formula MS 1542 840 627 (M + H) 1543 841 560 (M + H) 1544 842 634 (M + H) 1545 843 593 (M + H)

[2033] 174 TABLE 174 Ex. No. Formula MS 1546 844 627 (M + H) 1547 845 627 (M + H) 1548 846 560 (M + H) 1549 847 634 (M + H)

[2034] 175 TABLE 175 Ex. No. Formula MS 1550 848 627 (M + H) 1551 849 560 (M + H) 1552 850 532 (M + H) 1553 851 565 (M + H)

[2035] 176 TABLE 176 Ex. No. Formula MS 1554 852 599 (M + H) 1555 853 599 (M + H) 1556 854 532 (M + H) 1557 855 532 (M + H)

[2036] 177 TABLE 177 Ex. No. Formula MS 1558 856 584 (M + H) 1559 857 570 (M + H)

[2037] 178 TABLE 178 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 2 0.079 67 0.26 6 0.034 68 0.28 9 0.019 70 0.19 11 0.53 71 0.62 12 0.60 77 0.51 17 0.047 81 0.18 20 0.042 82 0.097 26 0.033 83 0.52 30 0.052 85 0.17 43 0.58 86 0.13 44 0.95 87 0.80 45 0.40 88 0.092 46 0.47 89 0.34 47 0.54 90 0.20 48 0.44 91 0.53 49 0.94 93 0.16 50 0.54 94 0.084 51 1.0 96 0.25 54 0.56 97 0.16 55 0.36 98 0.30

[2038] 179 TABLE 179 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 99 0.53 120 0.16 100 0.78 121 0.19 101 0.14 122 0.51 103 0.17 123 0.10 104 0.073 124 0.091 105 0.076 125 0.12 106 0.40 128 0.14 107 0.11 129 0.12 108 0.21 130 0.16 109 0.11 131 0.046 110 0.24 132 0.055 111 0.14 133 0.12 112 0.11 134 0.071 113 0.071 139 0.26 114 0.56 140 0.11 115 0.17 141 0.43 116 0.37 142 0.055 117 0.075 143 0.053 118 0.14 144 0.19 119 0.13 145 0.088

[2039] 180 TABLE 180 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 146 0.043 167 0.033 147 0.31 168 0.078 148 0.038 169 0.15 149 0.15 170 0.048 150 0.24 171 0.050 151 0.20 172 0.10 153 0.19 173 0.14 154 0.076 174 0.030 155 0.53 175 0.29 156 0.23 176 0.053 157 0.16 177 0.077 158 0.11 178 0.052 159 0.13 179 0.63 160 0.24 180 0.11 161 0.062 181 0.71 162 0.43 182 0.021 163 0.15 183 0.017 164 0.16 184 0.018 165 0.58 185 0.11 166 0.055 186 0.37

[2040] 181 TABLE 181 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 187 0.056 207 0.081 188 0.038 208 0.039 189 0.017 209 0.12 190 0.020 210 0.31 191 0.43 211 0.059 192 0.22 212 0.23 193 0.13 213 0.10 194 0.52 214 0.059 195 0.023 215 0.078 196 0.20 216 0.084 197 0.11 217 0.058 198 0.044 218 0.033 199 0.11 219 0.13 200 0.10 220 0.073 201 0.14 221 0.058 202 0.095 222 0.041 203 0.063 223 0.21 204 0.16 225 0.014 205 0.077 227 0.045 206 0.05 228 0.18

[2041] 182 TABLE 182 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 229 0.022 257 0.074 230 0.17 259 0.10 231 0.073 260 0.27 232 0.015 262 0.013 233 0.028 263 0.035 234 0.022 264 <0.01 235 0.036 265 0.014 236 0.075 266 0.018 237 0.015 267 0.014 238 0.19 268 0.012 239 0.17 269 0.013 240 0.055 270 0.012 248 0.012 271 0.024 249 0.022 272 0.066 250 0.018 273 0.041 252 0.32 276 0.023 253 0.65 279 0.017 254 0.038 280 0.016 255 0.038 281 0.052 256 0.079 282 0.019

[2042] 183 TABLE 183 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 283 0.014 300 0.045 284 0.014 301 0.017 285 0.012 303 0.10 286 0.014 304 0.017 287 0.012 305 0.01 288 0.013 306 0.013 289 <0.01 307 0.022 290 0.012 308 0.023 291 0.016 311 0.16 292 0.015 312 0.023 293 0.034 313 0.025 294 0.032 314 0.097 295 0.045 315 0.028 296 0.034 316 0.022 297 0.022 317 0.032 298 0.011 318 0.012 299 0.018 319 0.030

[2043] 184 TABLE 184 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 320 0.036 328 0.015 321 0.015 329 0.047 322 0.016 330 0.011 323 0.018 331 0.017 324 0.027 332 0.023 325 0.019 333 0.016 326 0.018 334 0.016 327 0.019 335 0.013

[2044] 185 TABLE 185 Example No. 249 1H NMR(&dgr;) ppm 858 300 MHz, DMSO-d6 8.02(1W d,J=1.5 Hz),8.11 (1H, d, J=1.8 Hz), 7.96-7.81 (3H, m), 7.67 (1H, s), 7.61-7.49(6H, m), 7.08 (2H, d, J=8.6 Hz), 5.19 (2H, s), 4.25 (1H, m), 2.38-2.17(2H, m),1.96-1.78 (4H, m), 1.70-1.56 (1H, m), 1.46-1.16 (3H, m), 1.11(9H, s) Purity >90% (NMR) MS 672 (M + 1) Example No. 250 1H NMR(&dgr;) ppm 859 300 MHz, DMSO-d6 8.25 (1H, d, J=1.5 Hz) 8.16-8.08 (2H, m), 7.99-7.88 (2H, m), 7.66(2H, d, J=8.6 Hz), 7.60-7.48(5H, m), 7.19 (2H, d, J=8.6 Hz), 5.17(2H, s), 4.31 (1H, m), 2.39-2.20 (2H, m), 2.04-1.79 (4H, m), 1.72-1.60 (1H, m), 1.50-1.18(3H, m) Purity >90% (NMR) MS 616(M + 1) Example No. 251 1H NMR(&dgr;) ppm 860 300 MHz, DMSO-d6 cis and trans mixture 8.13 and 8.11 (total 1H, each s), 7.90-7.74(2H, m), 7.42-7.22(5H, m), 4.56 and 4.52(total 2H, each s), 4.42(1H, brs), 3.78-3.06(2H, m) 2.33-1.33(18H, m) Purity >90% (NMR) MS 433 (M + 1)

[2045] 186 TABLE 186 Example No. 252 1H NMR(&dgr;) ppm 861 300 MHz, DMSO-d6 8.20(1H, d, J=1.85 Hz), 7.96 (1H, d, J=8.86 Hz), 7.84(1H, dd, J=8.6, 1.85 Hz), 7.54(2H, d, J=6.9 Hz), 7.48-7.26 (8H, m), 7.09 (1H, t, J=7.3 Hz), 5.43 (2H, s), 4.06(1H, m), 2.40-2.20(2H, m), 2.01-1.80(4H, m), 1.75-1.64 (1H, m), 1.51-1.28(3H, m) Purity >90% (NMR) MS 509 (M + 1) Example No. 253 1H NMR(&dgr;) ppm 862 300 MHz, DMSO-d6 8.21(1H, d, J=1.5 Hz), 7.93 (1H, d, J=8.7 Hz), 7.85 (1H, dd, J=8.4, 1.5Hz), 7.54-7.47(2H, m), 7.40-7.24(6H, m), 7.15(1H, d, J=3.6 Hz), 7.11-7.05(1H, m), 6.81(1H, d, J=3.6 Hz), 5.26(2H, s), 4.96(1H, m), 2.32-2.13(2H, m), 1.95-1.72(4H, m), 1.68-1.55(1H, m), 1.43-1.18(3H, m) Purity >90% (NMR) MS 493 (M + 1) Example No. 254 1H NMR(&dgr;) ppm 863 300 MHz, DMSO-d6 8.25(1H, s), 8.02(1H, d, J=8.7 Hz), 7.90(1H, dd, J=8.4, 1.4 Hz), 7.80-7.71 (2H, m), 7.67(2H, d, J=8.7 Hz), 7.33(2H, t, J=8.7 Hz), 7.26(2H, d, J=8.7 Hz), 5.46(2H, s), 4.78 (2H, s), 4.31(1H, m), 2.39-2.19(2H, m), 2.03-1.79(4H, m), 1.71-1.59(1H, m), 1.50-1.17(3H, m) Purity >90% (NMR) MS 558 (M + 1)

[2046] 187 TABLE 187 Example No. 255 1H NMR(&dgr;) ppm 864 300 MHz, DMSO-d6 8.34 (1H, s) 8.32 (1H, d, J=8.8 Hz), 8.09-8.03(3H, m), 7.83(2H, d, J=8.3 Hz), 7.79(2H, d, J=8.8 Hz), 7.36(2H, d, J=8.8 Hz), 5.54(2H, s), 4.38(1H, M), 2.74(3H, s), 2.40-2.18(2H, m), 2.13-1.96(2H, m), 1.93-1.78(2H, m), 1.73-1.57(1H, m), 1.55-1.15(3H, m) Purity >90% (NMR) MS 568(M + 1) Example No. 256 1H NMR(&dgr;) ppm 865 300 MHz, DMSO-d6 12.67(1H, brs), 8.23(1H, s), 7.94 and 7.87(2H, ABq, J=8.6 Hz), 7.79(1H, dd, J=8.7, 5.4 Hz), 7.62-7.41 (7H, m), 6.80(1H, dd, J=11.9, 2.3 Hz), 6.69(1H, dd, J=8.1, 2.1 Hz), 5.20(2H, s), 3.93(1H, brt, J=15.3Hz), 2.30-2.11(2H, brm) 1.88-1.74(4H, brm), 1.64-1.58(1H, brm), 1.41-1.14(3H, brm) Purity >90% (NMR) MS 585(M + 1) Example No. 257 1H NMR(&dgr;) ppm 866 300 MHz, DMSO-d6 8.19(1H, d, J=8.7 Hz), 7.93(H, s), 7.83-7.71(3H, m), 7.50-7.39(4H, m), 7.34-7.10(4H, m), 7.06(1H, dd, J=8.4, 2.9 Hz), 5.09(2H, s), 4.34(1H, m), 3.82(3H, s), 2.39-2.19(2H, m), 2.11-1.98(2H, m), 1.94-1.79(2H, m), 1.74-1.58 (1H, m), 1.52-1.21(3H, m) Purity >90% (NMR) MS 603(M + 1)

[2047] 188 TABLE 188 Example No. 258 1H NMR (&dgr;) ppm 867 300 MHz, DMSO-d6 7.79(1H, d, J=6.7 Hz), 7.56 (1H, d, J=7.5 Hz), 7.49 (2H, d, J=8.6 Hz), 7.42 (4H, s), 7.32-7.23 (3H, m), 7.09-7.03 (3H, m), 5.02 (2H, s), 4.46 (1H, m, 3.82 (3H, s), 1.95-1.83 (2H, m), 1.75-1.44 (5H, m), 1.30-1.10 (2H, m), 0.89-0.71 (1H, m) Purity >90% (NMR) MS 567 (M + 1) Example No. 259 1H NMR (&dgr;) ppm 868 300 MHz, DMSO-d6 8.93 (2H, d, J=6.6 Hz), 8.36 (1H, s), 8.28 (1H, d, J=8.7 Hz), 8.10-8.03 (3H, m), 7.85 (2H, d, J=8.7 Hz), 7.33 (2H, d, J=8.7 Hz), 7.23 (1H, s), 7.23 (1H, s), 6.81 (1H, s), 5.56 (2H, s), 4.39 (1H, m), 2.97, 2.92 (6H, s), 2.40-2.18 (2H, m), 2.16-1.95 (2H, m), 1.90-1.75 (2H, m), 1.70-1.55 (1H, m), 1.50-1.15 (3H, m) Purity >90% (NMR) MS 591 (M + 1) Example No. 260 1H NMR (&dgr;) ppm 869 300 MHz, DMSO-d6 8.93 (2H, d, J=6.3 Hz), 8.35 (1H, s), 8.26 (1H, d, J=8.7 Hz), 8.09-8.02 (3H, m), 7.86 (2H, d, J=8.7 Hz), 7.50 (1H, s), 7.35 (2H, d, J=8.4 Hz), 7.24 (2H, d, J=7.8 Hz), 5.60 (2H, s), 4.39 (1H, m), 2.50-2.18 (2H, m), 2.15-1.95 (2H, m), 1.90-1.75 (2H, m), 1.70-1.55 (1H, m) 1.50-1.10 (3H, m) Purity >90% (NMR) MS 564 (M + 1)

[2048] 189 TABLE 189 Example No. 261 1H NMR (&dgr;) ppm 870 300 MHz, DMSO-d6 8.22 (1H, d, J=7.8 Hz), 7.85 (1H, d, J=6.7 Hz), 7.63 (2H, d, J=9.0 H), 7.51-7.38 (5H, m), 7.29 (1H, d, J=8.3 Hz), 7.23 (1H, d, J=3.0 Hz), 7.06 (2H, d, J=9.0 Hz), 7.06 (1H, dd, J=8.6, 3.0 Hz), 5.05 (2H, s), 4.41-4.25 (1H, m), 3.83 (3H, s), 2.40-2.20 (2H, m), 2.03-1.78 (4H, m), 1.72-1.57 (1H, m), 1.50-1.18 (3H, m) Purity >90% (NMR) MS 567 (M + 1) Example No. 262 1H NMR (&dgr;) ppm 871 300 MHz, DMSO-d6 8.29 (1H, d, J=1.5 Hz), 8.26 (1H, d, J=9.0 Hz), 8.19 (1H, d, J=1.8 Hz), 8.13 (1H, brs), 8.08-7.96 (2H, m), 7.73 (2H, d, J=9.0 Hz), 7.57-7.43 (6H, m), 7.24 (2H, d, J=9.0 Hz), 5.14 (2H, s), 4.36 (1H, m), 2.38-2.18 (2H, m), 2.12-1.97 (2H, m), 1.93-1.80 (2H, m), 1.73-1.58 (1H, m), 1.50-1.20 (3H, m) Purity >90% (NMR) MS 580 (M + 1) Example No. 263 1H NMR (&dgr;) ppm 872 300 MHz, DMSO-d6 12.85 (1H, brs), 8.72 (1H, d, J=4.8 Hz), 8.22 (1H, s), 8.14 (1H, d, J=6.3 Hz), 8.03 and 7.76 (4H, ABq, J=8.6 Hz), 7.93 and 7.85 (2H, A′ B′ q, J=8.6 Hz), 7.60 and 7.15 (4H, ABq, J=8.7 Hz), 7.55 (1H, dd, J=6.3, 4.8 Hz), 5.19 (2H, s), 4.26 (1H, brt, J=12.6 Hz), 2.35-2.18 (2H, brm), 1.95-1.77 (4H, brm), 1.70-1.60 (1H, brm), 1.45-1.15 (3H, brm) Purity >90% (NMR) MS 548 (M + 1)

[2049] 190 TABLE 190 Example No. 264 1H NMR (&dgr;) ppm 873 300 MHz, DMSO-d6 8.23 (1H, d, J=1.0 Hz), 7.92 (1H, dd, J=8.7, 1.0 Hz), 7.87 (1H, d, J=8.7 Hz), 7.60 (2H, d, J=8.6 Hz), 7.47 (2H, d, J=8.7 Hz), 7.44 (2H, d, J=8.7 Hz), 7.30 (1H, d, J=8.3 Hz), 7.23 H, d, J=2.6 Hz), 7.11 (2H, d, J=8.7 Hz), 7.06 (1H, dd, J=8.7, 2.6 Hz), 5.04 (2H, s), 4.36 (1H, m), 3.83 (3H, s), 2.80-2.70 (4H, m), 2.60-2.40 (2H, m), 2.30-2.20 (2H, m) Purity >90% (NMR) MS 586, 588 (M + 1) Example No. 265 1H NMR (&dgr;) ppm 874 300 MHz, DMSO-d6 8.30 (1H, d, J=1.5 Hz), 8.25 (1H, d, J=9.1 Hz), 8.03 (1H, dd, J=8.7, 1.5 Hz), 7.76-7.96 (3H, m), 7.55-7.49 (5H, m), 7.42 (1H, d, J=7.6 z), 7.23 (2H, d, J=8.7 Hz), 5.15 (2H, s), 4.35 (1H, m), 3.01 (3H, s), 2.97 (3H, s), 2.37-2.20 (2H, m), 2.09-1.97 (2H, m), 1.94-1.81 (2H, m), 1.72-1.60 (1H, m), 1.50-1.21 (3H, m) Purity >90% (NMR) MS 608 (M + 1) Example No. 266 1H NMR (&dgr;) ppm 875 300 MHz, DMSO-d6 8.27 (1H, d, J=1.5 Hz), 8.20 (1H, d, J=9.0 Hz), 8.00 (1H, dd, J=8.6, 1.5 Hz), 7.82 (2H, d, J=8.2 Hz), 7.76-7.65 (5H, m), 7.56 (1H, dd, J=7.9, 1.8 Hz), 7.47 (1H, d, J=7.5 Hz), 7.20 (2H, d, J=8.6 Hz), 5.16 (2H, s), 4.32 (1H, m), 3.02 (3H, s), 2.98 (3H, s), 2.38-2.19 (2H, m), 2.07-1.95 (2H, m), 1.93-1.80 (2H, m), 1.72-1.58 (1H, m), 1.52-1.18 (3H, m) Purity >90% (NMR) MS 642 (M + 1)

[2050] 191 TABLE 191 Example No. 267 1H NMR (&dgr;) ppm 876 300 MHz, DMSO-d6 8.34 (2H, m), 8.03 (1H, d, J=8.3 Hz), 7.77-7.68 (3H, m), 7.54-7.40 (4H, m), 7.33 (2H, d, J=8.6 Hz), 7.24 (2H, d, J=9.0 Hz), 5.16 (2H, s), 4.36 (1H, m), 3.01 (3H, s), 2.97 (3H, s), 2.40-2.20 (2H, m), 2.11-1.97 (2H, m), 1.93-1.81 (2H, m), 1.71-1.60 (1H, m), 1.50-1.21 (3H, m) Purity >90% (NMR) MS 620 (M + 1) Example No. 268 1H NMR (&dgr;) ppm 877 300 MHz, DMSO-d6 8.67-8.59 (1H, m), 8.30 (1H, s), 8.13-8.20 (2H, m), 8.02-7.92 (2H, m), 7.65 (1H, t, J=8.3 Hz), 7.56-7.45 (5H, m), 7.18 (1H, dd, J=12.0, 2.2 Hz), 7.05 (1H, dd, J=8.6, 2.2 Hz), 5.14 (2H, s), 4.09 (1H, m), 2.82 (3H, d, J=4.5 Hz), 2.34-2.12 (2H, m), 1.99-1.79 (4H, m), 1.71-1.59 (1H, m), 1.49-1.21 (3H, m) Purity >90% (NMR) MS 612 (M + 1) Example No. 269 1H NMR (&dgr;) ppm 878 300 MHz, DMSO-d6 8.29 (1H, s), 8.13 (1H, d, J=9.0 Hz), 7.97 (1H, dd, J=8.6, 1.5 Hz), 7.71 (1H, d, J=1.8 Hz), 7.63 (1H, t, J=8.2 Hz), 7.56-7.41 (6H, m), 7.17 (1H, dd, J=12.0, 2.2 Hz), 7.03 (1H, dd, J=8.2, 1.8 Hz), 5.14 (2H, s), 4.15-4.00 (1H, m), 3.01 (3H, s), 2.98 (3H, s), 2.32-2.13 (2H, m) 1.95-1.79 (4H, m), 1.72-1.59 (1H, m), 1.45-1.21 (3H, m) Purity >90% (NMR) MS 626 (M + 1)

[2051] 192 TABLE 192 Example No. 270 1H NMR (&dgr;) ppm 879 300 MHz, DMSO-d6 8.24 (1H, d, J=1.4 Hz), 8.19 (1H, d, J=1.8 Hz), 8.11 (1H, brs), 8.02-7.85 (3H, m), 7.60-7.44 (7H, m), 7.10 (1H, dd, J=12.0, 2.1 Hz), 6.98 (1H, dd, J=8.4, 2.1 Hz), 5.11 (2H, s), 3.98 (1H, m), 2.30-2.12 (2H, m), 1.91-1.73 (4H, m), 1.71-1.58 (1H, m), 1.45-1.15 (3H, m) Purity >90% (NMR) MS 598 (M + 1) Example No. 271 1H NMR (&dgr;) ppm 880 300 MHz, DMSO-d6 8.29 (1H, d, J=1.5 Hz), 8.24 (1H, d, J=8.7 Hz), 8.07-7.98 (3H, m), 7.80-7.68 (5H, m), 7.56 (1H, dd, J=8.0, 1.8 Hz), 7.47 (1H, d, J=8.0 Hz), 7.21 (2H, d, J=8.4 Hz), 5.18 (2H, s), 4.34 (1H, m), 3.27 (3H, s), 3.02 (3H, s), 2.98 (3H, s), 2.38-2.18 (2H, m), 2.10-1.95 (2H, m), 1.93-1.79 (2H, m), 1.72-1.59 (1H, m), 1.50-1.19 (3H, m) Purity >90% (NMR) MS 652 (M + 1) Example No. 272 1H NMR (&dgr;) ppm 881 300 MHz, DMSO-d6 8.97 (1H, d, J=1.8 Hz), 8.85 (1H, d, J=4.7 Hz), 8.46 (1H, d, J=8.0 Hz), 8.39-8.26 (2H, m), 8.06 (1H, d, J=8.7 Hz), 7.99-7.64 (6H, m), 7.24 (2H, d, J=8.7 Hz), 5.25 (2H, s), 4.36 (1H, m), 3.03 (3H, s), 2.97 (3H, s), 2.39-2.19 (2H, m), 2.14-1.96 (2H, m), 1.94-1.78 (2H, m), 1.73-1.60 (1H, m), 1.21-1.55 (3H, m) Purity >90% (NMR) MS 575 (M + 1)

[2052] 193 TABLE 193 Example No. 273 1H NMR (&dgr;) ppm 882 300 MHz, DMSO-d6 8.30 (1H, s), 8.27(1H, d, J=8.7 Hz), 8.05 (1H, d, J=8.7 Hz), 7.77-7.67 (3H, m), 7.58-7.48 (6H, m), 7.22 (2H, d, J=8.4 Hz), 5.18 (2H, s), 4.35 (1H, brt, J=9.8 Hz), 3.06-2.88 (12H, brm), 2.38-2.20 (2H, brm), 2.08-1.96 (2H, brm), 1.90-1.80 (2H, brm), 1.70-1.60 (1H, brm), 1.49-1.22 (3H, brm) Purity >90% (NMR) MS 645 (M + 1) Example No. 274 1H NMR (&dgr;) ppm 883 300 MHz, DMSO-d6 mixture of cis and trans 8.35, 8.34 (1H, s), 8.15-8.10 (2H, m), 7.79-7.70 (3H, m), 7.49 (2H, d, J=8.7 Hz), 7.44 (2H, d, J=8.7 Hz), 7.31 (1H, d, J=8.4 Hz), 7.25-7.19 (2H, m), 7.07 (1H, d, J=8.5 Hz), 5.08 (2H, s), 4.75 (1H, m), 3.83 (3H, s), 3.70-1.90 (8H, m) Purity about 80% (NMR) MS 601 (M + 1) Example No. 275 1H NMR (&dgr;) ppm 884 300 MHz, DMSO-d6 8.33 (1H, s), 8.13 (1H, d, J=7.5 Hz), 7.93 (1H, d, J=8.8 Hz), 7.74 (2H, d, J=8.7 Hz), 7.49 (2H, d, J=8.6 Hz), 7.44 (2H, d, J=8.6 Hz), 7.31 (1H, d, J=8.5 Hz), 7.25-7.15 (3H, m), 7.07 (1H, d, J=8.5 Hz), 5.08 (2H, s), 4.98 (1H, m), 3.83 (3H, s), 3.65-3.45 (2H, m), 3.30-3.10 (2H, m), 3.00-2.75 (2H, m), 2.60-2.30 (2H, m) Purity >90% (NMR) MS 617 (M + 1)

[2053] 194 TABLE 194 Example No. 276 1H NMR (&dgr;) ppm 885 300 MHz, DMSO-d6 8.25 (1H, s), 7.93 and 7.87 (2H, ABq, J=9.1 Hz), 7.55 (1H, t, J=8.6 Hz), 7.48 and 7.42 (4H, A′ B′ q, J=8.6 Hz), 7.31 (1H, d, J=8.5 Hz), 7.24 (1H, d, J=2.6 Hz), 7.09-6.95 (3H, m), 5.05 (2H, s), 4.11 (1H, brt, J=14.0 Hz), 3.84 (3H, s), 2.83-2.67 (4H, brm), 2.50-2.32 (2H, brm), 2.21-2.10 (2H, brm) Purity >90% (NMR) MS 603 (M + 1) Example No. 277 1H NMR (&dgr;) ppm 886 300 MHz, DMSO-d6 cis and trans mixture 8.28 and 8.24 (total 1H, each s), 7.94-7.87 (1H, m), 7.60-7.41 (5H, m), 7.31 (1H, d, J=8.5 Hz), 7.23-7.21 (1H, m), 7.12-7.05 (2H, m), 7.00-6.95 (1H, m), 5.06 and 5.05 (total 2H, each s), 4.47 and 4.34 (total 1H, each brs), 3.83 (3H, s), 3.12-1.76 (8H, m) Purity >90% (NMR) MS 619 (M + 1) Example No. 278 1H NMR (&dgr;) ppm 887 300 MHz, DMSO-d6 12.9 (1H, brs), 8.27 (1H, s), 7.97 and 7.74 (2H, ABq, J=8.6 Hz), 7.58 (1H, t, J=8.6 Hz), 7.49 and 7.43 (4H, A′ B′ q, J=8.5 Hz), 7.31 (1H, d, J=8.5 Hz), 7.22 (1H, d, J=2.6 Hz), 7.13-6.92 (3H, m), 5.05 (2H, s), 4.67 (1H, brt, J=14.2 Hz), 3.57-3.40 (2H, brm), 3.20-3.05 (2H, brm), 2.91-2.70 (2H, brm), 2.28-2.11 (2H, brm) Purity >90% (NMR) MS 635 (M + 1)

[2054] 195 TABLE 195 Example No. 279 1H NMR (&dgr;) ppm 888 300 MHz, DMSO-d6 8.30 (1H, s), 8.23 (1H, d, J=8.7 Hz), 8.06-8.00 (2H, m), 7.83 (1H, dd, J=8.0, 1.8 Hz), 7.71 (2H, d, J=8.4 Hz), 7.64 (1H, d, J=8.0 Hz), 7.59-7.54 (4H, m), 7.22 (2H, d, J=8.4 Hz), 5.25 (2H, s), 4.33 (1H, m), 2.66 (3H, s), 2.66 (3H, s), 2.37-2.19 (2H, m), 1.93-1.80 (2H, m), 1.70-1.59 (1H, m), 1.47-1.21 (3H, m) Purity >90% (NMR) MS 644 (M + 1) Example No. 280 1H NMR (&dgr;) ppm 889 300 MHz, DMSO-d6 8.32-8.23 (3H, m), 8.08-8.01 (2H, m), 7.73 (2H, d, J=8.6 Hz), 7.65 (1H, d, J=8.2 Hz), 7.59-7.51 (4H, m), 7.25 (2H, d, J=8.6 Hz), 5.21 (2H, s), 4.34 (1H, m), 3.32 (3H, s), 2.37-2.19 (2H, m), 2.10-1.98 (2H, m), 1.93-1.80 (2H, m), 1.71-1.60 (1H, m), 1.51-1.21 (3H, m) Purity >90% (NMR) MS 615 (M + 1) Example No. 281 1H NMR (&dgr;) ppm 890 300 MHz, DMSO-d6 8.30 (1H, d, J=1.5 Hz), 8.24 (1H, s), 8.14 (1H, d, J=8.6 Hz), 8.07-7.95 (2H, m), 7.63 (1H, t, J=8.6 Hz), 7.57-7.47 (5H, m), 7.16 (1H, dd, J=12.0, 2.2 Hz), 7.03 (1H, dd, J=8.6, 2.2 Hz), 5.17 (2H, s), 4.06 (1H, m), 3.90 (3H, s), 2.31-2.11 (2H, m), 1.97-1.78 (4H, m), 1.71-1.59 (1H, m), 1.43-1.22 (3H, m) Purity >90% (NMR) MS 315

[2055] 196 TABLE 196 Example No. 282 1H NMR (&dgr;) ppm 891 300 MHz, DMSO-d6 8.36 (1H, s), 8.35 (1H, d, J=9.3 Hz), 8.09 (1H, d, J=9.3 Hz), 7.78 (2H, d, J=8.7 Hz), 7.48-7.25 (9H, m), 5.09 (2H, s), 4.39 (1H, m), 3.04 (6H, s), 2.40-2.15 (2H, m), 2.10-1.95 (2H, m), 1.90-1.75 (2H, m), 1.70-1.55 (1H, m), 1.50-1.20 (3H, m) Purity >90% (NMR) MS 580 (M + 1) Example No. 283 1H NMR (&dgr;) ppm 892 300 MHz, DMSO-d6 10.03 (1H, s), 8.33 (1H, s), 8.29 (1H, d, J=8.7 Hz), 8.06 (1H, d, J=9.0 Hz), 7.74 (2H, d, J=9.0 Hz), 7.51-7.42 (5H, m), 7.37-7.30 (2H, m), 7.22 (2H, d, J=8.7 Hz), 5.10 (2H, s), 4.37 (1H, m), 3.06 (3H, s), 2.40-2.18 (2H, m), 2.15-1.95 (2H, m), 1.90-1.80 (2H, m), 1.75-1.55 (1H, m), 1.50-1.20 (3H, m) Purity >90% (NMR) MS 630 (M + 1) Example No. 284 1H NMR (&dgr;) ppm 893 300 MHz, DMSO-d6 8.30 (1H, s), 8.14 (1H, d, J=8.7 Hz), 7.97 (1H, d, J=8.7 Hz), 7.96-7.41 (8H, m), 7.16 (1H, dd, J=12.4, 2.2 Hz), 7.03 (1H, dd, J=8.4, 2.2 Hz), 5.15 (2H, s), 4.15 (1H, m), 3.54-3.16 (4H, m), 2.33-2.13 (2H, m), 1.97-1.79 (4H, m), 1.70-1.02 (9H, m) Purity >90% (NMR) MS 654 (M + 1)

[2056] 197 TABLE 197 Example No. 285 1H NMR (&dgr;) ppm 894 300 MHz, DMSO-d6 8.37 (1H, d, J=7.3 Hz), 8.30 (1H, s), 8.19-8.12 (2H, m), 8.02-7.95 (2H, m), 7.65 (1H, t, J=8.4 Hz), 7.56-7.43 (5H, m), 7.18 (1H, dd, J=12.0, 1.8 Hz), 7.06 (1H, dd, J=8.4, 2.1 Hz), 5.13 (2H, s), 4.22-4.03 (2H, m), 2.34-2.13 (2H, m), 1.99-1.78 (4H, m), 1.72-1.57 (1H, m), 1.44-1.14 (3H, m), 1.20, 1.18 (6H, each s) Purity >90% (NMR) MS 640 (M + 1) Example No. 286 1H NMR (&dgr;) ppm 895 300 MHz, DMSO-d6 8.29 (1H, s), 8.13 (1H, d, J=8.7 Hz), 7.97 (1H, dd, J=8.7, 1.4 Hz), 7.69-7.40 (8H, m), 7.16 (1H, dd, J=12.0, 2.2 Hz), 7.02 (1H, dd, J=8.4, 2.2 Hz), 5.15 (2H, s), 4.07 (1H, m), 3.71-3.23 (2H, m), 1.98-1.71 (4H, m), 1.71-1.18 (10H, m) Purity >90% (NMR) MS 666 (M + 1) Example No. 287 1H NMR (&dgr;) ppm 896 300 MHz, DMSO-d6 8.29 (1H, s), 8.13 (1H, d, J=8.0 Hz), 7.97 (1H, d, J=8.4 Hz), 7.83 (1H, s), 7.68-7.41 (7H, m), 7.17 (1H, d, J=12.0 Hz), 7.03 (1H, d, J=8.4 Hz), 5.15 (2H, s), 4.07 (1H, m), 3.58-3.41 (4H, m), 2.34-2.13 (2H, m), 1.97-1.77 (8H, m), 1.71-1.58 (1H, m), 1.49-1.18 (3H, m) Purity >90% (NMR) MS 652 (M + 1)

[2057] 198 TABLE 198 Example No. 288 1H NMR (&dgr;) ppm 897 300 MHz, DMSO-d6 8.62(1N, m), 8.31 (1H, s), 8.22-8.14 (2H, m), 8.99 (2H, d, J=8.7 Hz), 7.66 (1H, t, J=7.7 Hz), 7.58-7.44 (5H, m), 7.19 (1H, dd, J=8.7, 2.2 Hz), 5.14 (2H, s), 4.11 (1H, m), 3.67-3.49 (2H, m), 3.45-3.30 (2H, m), 2.37-2.12 (2H, m), 2.00-1.76 (4H, m), 1.70-1.58 (1H, m), 1.48-1.17 (3H, m) Purity >90% (NMR) MS 642 (M + 1) Example No. 289 1H NMR (&dgr;) ppm 898 400 MHz, DMSO-d6 8.28 (1H, s), 8.11 (1H, d, J=8.9 Hz), 7.96 (1H, d, J=8.9 Hz), 7.68 (1H, s), 7.62 (1H, t, J=8.2 Hz), 7.55-7.41 (6H, m), 7.15 (1H, d, J=11.7 Hz), 7.02 (1H, d, J=8.4 Hz), 5.14 (2H, s), 4.12-3.13 (6H, m), 2.30-1.19 (13H, m) Purity >90% (NMR) MS 682 (M + 1) Example No. 290 1H NMR (&dgr;) ppm 899 400 MHz, DMSO-d6 8.29 (1H, s), 8.15 (1H, d, J=8.6 Hz), 7.98 (1H, d, J=8.8 Hz), 7.72 (1H, s), 7.64 (1H, t, J=8.8 Hz), 7.57-7.43 (6H, m), 7.18 (1H, dd, J=12.1, 2.1 Hz), 7.03 (1H, d, J=10.7 Hz), 5.12 (2H, s), 4.15-4.01 (1H, m), 3.75-3.33 (8H, m), 2.31-2.14 (2H, m), 1.96-1.78 (4H, m), 1.70-1.58 (1H, m), 1.47-1.21 (3H, m) Purity >90% (NMR) MS 668 (M + 1)

[2058] 199 TABLE 199 Example No. 291 1H NMR (&dgr;) ppm 900 400 MHz,DMSO-d6 8.29 (1H, s), 8.14 (1H, d, J=8.9 Hz), 7.97 (1H, d, J=8.6 Hz), 7.71 (1H, s), 7.63 (1H, t, J=8.2 Hz), 7.56-7.42 (6H, m), 7.17 (1H, d, J=12.3 Hz), 7.03 (1H, d, J=10.7 Hz), 5.14 (2H, s), 4.07 (1H, m), 3.96-3.52 (4H, m), 2.79-2.56 (4H, m), 2.32-2.14 (2H, m), 1.97-1.79 (4H, m), 1.71-1.58 (1H, m), 1.51-1.19 (3H, m) Purity >90% (NMR) MS 684 (M + 1) Example No. 292 1H NMR (&dgr;) ppm 901 300 MHz, DMSO-d6 9.07-8.99 (1H, m), 8.30 (1H, s), 8.23-8.12 (2H, m), 8.04-7.95 (2H, m), 7.65 (1H, t, J=8.2 Hz), 7.60-7.45 (5H, m), 7.19 (1H, dd, J=12.0, 2.6 Hz), 7.06 (1H, dd, J=8.6, 2.2 Hz), 5.16 (2H, s), 4.18-4.02 (1H, m), 3.97 (2H, d, J=6.0 Hz), 2.33-2.14 (2H, m), 1.99-1.79 (4H, m), 1.72-1.59 (1H, m), 1.45-1.19 (3H, m) Purity >90% (NMR) MS 656 (M + 1) Example No. 293 1H NMR (&dgr;) ppm 902 300 MHz, DMSO-d6: 8.21 (1H, s), 7.94 and 7.86 (2H, ABq, J=8.6 Hz), 7.72 (1H, d, J=2.4 Hz), 7.59 and 7.11 (4H, A′ B′ q, J=8.9 Hz), 7.53 (1H, dd, J=8.4, 2.4 Hz), 7.38 (1H, d, J=8.4 Hz), 7.36 and 7.32 (4H, A″B″q, J=8.1 Hz), 5.07 (2H, s), 4.27 (1H, brt, J=13.8 Hz), 2.87 (2H, t, J=7.8 Hz), 2.57 (2H, t, J=7.8 Hz), 2.35-2.20 (2H, brm), 1.96-1.79 (4H, brm), # 1.68-1.59 (1H, brm), 1.47-1.18 (3H, brm) Purity >90% (NMR), MS 637 (M + 1)

[2059] 200 TABLE 200 Example No. 294 1H NMR (&dgr;) ppm 903 300 MHz, DMSO-d6 8.30 (1H, s), 8.25 and 8.03 (2H, ABq, J=8.9 Hz), 7.73 (1H, s), 7.73 (2H, d, J=8.6 Hz), 7.55 (1H, dd, J=8.0, 2.3 Hz), 7.40 (4H, s), 7.39 (1H, d, J=8.0 Hz), 7.23 (2H, d, J=8.6 Hz), 5.11 (2H, s), 4.55 (2H, s), 4.36 (1H, brt, J=14.8 Hz), 2.37-2.19 (2H, brm), 2.09-1.96 (2H, brm), 1.91-1.79 (2H, brm), 1.71-1.59 (1H, brm), 1.50-1.20 (3H, brm) Purity >90% (NMR) MS 567 (M + 1) Example No. 295 1H NMR (&dgr;) ppm 904 300 MHz, DMSO-d6 8.30 (1H, s), 8.25 and 8.04 (2H, ABq, J=8.7 Hz), 7.74 (1H, s), 7.72 (2H, d, J=8.7 Hz), 7.56 (1H, d, J=8.7 Hz), 7.48-7.35 (5H, m), 7.22 (2H, d, J=8.7 Hz), 5.11 (2H, s), 4.46 (2H, s), 4.35 (1H, brt, J=14.8 Hz), 3.31 (3H, s), 2.37-2.17 (2H, brm), 2.07-1.95 (2H, brm), 1.92-1.79 (2H, brm), 1.73-1.56 (1H, brm), 1.52-1.20 (3H, brm) Purity >90% (NMR) MS 581 (M + 1) Example No. 296 1H NMR (&dgr;) ppm 905 300 MHz, DMSO-d6 8.21 (1H, d, J=1.5 Hz), 7.98 (1H, d, J=1.2 Hz), 7.97-7.91 (2H, m), 7.84 (1H, dd, J=8.7, 1.5 Hz), 7.77 (1H, d, J=2.1 Hz), 7.70 (1H, d, J=7.5 Hz), 7.60-7.54 (4H, m), 7.43 (1H, d, J=8.4 Hz), 7.09 (2H, d, J=8.7 Hz), 5.05 (2H, s), 4.25 (1H, brt, J=14.8 Hz), 2.36-2.18 (2H, brm), 1.95-1.79 (4H, brm), 1.71-1.6 (1H, brm), 1.43-1.18 (3H, brm) Purity >90% (NMR) MS 581 (M + 1)

[2060] 201 TABLE 201 Example No. 297 1H NMR (&dgr;) ppm 906 300 MHz, DMSO-d6 12.7 (1H, brs), 8.21 (1H, s), 7.94 and 7.85 (2H, ABq, J=8.6 Hz), 7.60-7.55 (3H, m), 7.49 and 7.45 (4H, A′ B′ q, J=8.3 Hz), 7.12 (2H, d, J=8.7 Hz), 5.05 (2H, s), 4.26 (1H, brt, J=13.0 Hz), 2.54 (3H, s), 2.38-2.20 (2H, brm), 1.97-1.80 (4H, brm), 1.71-1.59 (1H, brm), 1.47-1.20 (3H, brm) Purity >90% (NMR) MS 583 (M + 1) Example No. 298 1H NMR (&dgr;) ppm 907 300 MHz, DMSO-d6 8.22 (1H, s), 8.01 (1H, s), 7.95 and 7.86 (2H, ABq, J=8.6 Hz), 7.79 (1H, d, J=7.8 Hz), 7.58 (3H, t, J=7.5 Hz), 7.53 (4H, s), 7.13 (2H, d, 8.7 Hz), 5.15 (2H, s), 4.26 (1H, brt, J=13.8 Hz), 2.83 (3H, s), 2.37-2.18 (2H, brm), 1.95-1.78 (4H, brm), 1.70-1.59 (1H, brm), 1.47-1.17 (3H, brm) Purity >90% (NMR) MS 599 (M + 1) Example No. 299 1H NMR (&dgr;) ppm 908 300 MHz, DMSO-d6 8.43-8.16 (3H, m), 8.07-7.94 (2H, m), 7.72 (2H, d, J=8.6 Hz), 7.62-7.49 (5H, m), 7.23 (2H, d, J=8.6 Hz), 5.16 (2H, s), 4.34 (1H, m), 2.39-2.20 (2H, m), 2.10-1.96 (2H, m), 1.93-1.80 (2H, m), 1.71-1.58 (1H, m), 1.49-1.19 (3H, m) Purity >90% (NMR) MS 562 (M + 1)

[2061] 202 TABLE 202 Example No. 300 1H NMR (&dgr;) ppm 909 300 MHz, DMSO-d6: 2.77(1H, brs), 8.83 (2H, d, J=1.9 Hz), 8.56 (2H, dd, J=4.9, 1.9 Hz), 8.22 (1H, d, J=1.5 Hz), 7.97 (2H, dt, J=7.9, 1.9 Hz), 7.95 (1H, d, J=8.6 Hz), 7.87 (1H, dd, J=8.6, 1.5 Hz), 7.57 (1H, t, J=8.7 Hz), 7.46 (2H, dd, J=7.9, 4.9 Hz), 7.26 (1H, dd, J=12.0, 4.9 Hz), 7.14 (1H, dd, J=8.8, 2.3 Hz), 6.99 (2H, s), 3.94 (1H, brt), 2.26-2.09 (2H, m), 1.87-1.73 (4H, m), 1.67-1.57 (1H, # m), 1.42-1.12 (3H, m) Purity >90% (NMR) MS 523 (M + 1) Example No. 301 1H NMR (&dgr;) ppm 910 300 MHz, DMSO-d6 8.22 (1H, s), 7.95(1H, d, J=8.7 Hz), 7.87 (1H, dd, J=1.5 Hz, 9.0 Hz), 7.62 (4H, d, J=8.4 Hz), 7.55 (1H, t, J=9.0 Hz), 7.44 (4H, d, J=8.1 Hz), 7.20 (1H, dd, J=2.1 Hz, 12.0 Hz), 7.11 (1H, dd, J=2.1 Hz, 8.7 Hz), 6.86 (1H, s), 3.94 (1H, m), 2.96, 2.88 (12H, s), 2.35-2.00 (2H, m), 1.95-1.70 (4H, m), 1.65-1.50 (1H, m), 1.45-1.10 (3H, m) Purity >90% (NMR) MS 663 (M + 1) Example No. 302 1H NMR (&dgr;) ppm 911 300 MHz, DMSO-d6 8.14 (1H, s), 7.88 (1H, d, J=8.4 Hz), 7.68 (1H, d, J=8.7 Hz), 7.64-7.55 (3H, m), 7.50 (1H, t, J=8.7 Hz), 7.22-7.17 (3H, m), 7.11 (1H, s), 7.08-7.00 (2H, m), 3.90 (1H, m), 2.15-2.00 (2H, m), 1.95-1.50 (5H, m), 1.45-1.00 (3H, m) Purity >90% (NMR) MS 532 (M + 1)

[2062] 203 TABLE 203 Example No. 303 1HNMR(&dgr;)ppm 912 300MHz, CDCl3 8.49(1H, s), 7.98(1H, dd, J=8.6, 1.5Hz), 7.71(1H, d, J=1 .8Hz), 7.66(1H, d, J=8.6Hz), 7.55-7.29 (7H, m), 6.80(1H, dd, J=8.2, 2.2Hz), 6.69(1H, dd, J=11.2, 2.211z), 4.99(2 H, s), 4.10-3.92(1H, m), 3.9 5(3H, s), 3.15(3H, s), 3.06 (3H, s), 2.31-2.14(2H, m), 2.04-1.86(4H, m), 1.81-1.71 # 1H, m), 1.41-1.21(3H, m) Purity > 90% (NMR) MS 640(M + 1) Example No. 304 1HNMR(&dgr;) ppm 913 300MHz, DMSO-d6 8.21(1H, s), 7.94(1H,d,J=8.7 7Hz), 7.84(1H, d, J=9.1Hz), 7.70(1H, s), 7.26-7.39(9H, m), 7.11(2H, d, J=8.4Hz), 5.11(2H, s), 4.26(1H, m), 3.01 (3H, s), 2.97(3H, s), 2.38-2.19(2H, m), 1.97-1.78(4H, m), 1.72-1.57(1H, m), 1.48-1.17(3H, m) Purity > 90%(NMR) MS 608(M + 1) Example No. 305 1HNMR(&dgr;) ppm 914 300MHz, DMSO-d6 8.24(2H. s), 8.03(1H, d, J=8.0Hz), 7.96(1H, d, J=8.8Hz), 7.87(1H, d, J=9.1Hz), 7.60-7.46(6H, m), 7.09(1H, dd, J=12.0, 1.8Hz), 6.97(1H, dd, J=8.4, 1.8Hz), 5.16(2H, s), 3.97(1H, m), 2.31-2.11(2H, m), 1.92-1.73(4H, m), 1.70-1.57(1H, m), 1.46-1.13(3H, m) Purity > 90% (NMR) MS 599 (M + 1)

[2063] 204 TABLE 204 Example No. 306 1HNMR(&dgr;) ppm 915 3H300MHz, DMSO-d6 12.84(1H, brs), 8.21(1H, s), 7.98-7.84(5H, m), 7.58(2H, d, J=8.7Hz), 7.54(2H, d, J=7.8Hz), 7.34(1H, , d, J=8.7H z), 7.26(1H, d, J=2.4Hz), 7.13-7.06(3H, m), 5.06(2H, s), 4.26(1H, brt, J=12.7Hz), 3.84(3H, s), 2.36-2.17(2H, b rm), 1.99-1.80(4H, brm), 1.73-1.59(1H, brm), 1.47- #1.17(3H, brm) Purity >90% (NMR) MS 577 (M+1) Example No. 307 1HNMR(&dgr;) ppm 916 3H300MHz, DMSO-d6 8.22(1H, s), 8.04(1H, s), 7.96(2H, d, J=8.1Hz), 7.87(2H, s), 7.72(1H, d, J=1.2Hz), 7.59-7.41(7H, m), 5.12(2H, s), 4.25(1H, brt, J=11.8Hz), 3.02(3H, brs), 2.98(3H, brs), 2.38-2.15(2H, brm), 1.93-1.76(4H, brm),1.71-1.59 (1H, brm), 1.46-1.16(3H, brm) Purity >90% (NMR) MS 617(M+1) Example No. 308 1HNMR(&dgr;) ppm 917 3H300MHz, DMSO-d6 8.27(1H, s), 8.08(1H, d, J=9.0 Hz), 7.93(1H, d, J=8.7Hz), 7.65(2H, d, J=8.7Hz), 7.46 (2H, d, J=8.1Hz), 7.42(2H, d, J=8.4Hz), 7.30-7.04(5H, m), 5.03(2H, s) 4.32(1H m), 2.40-2.10(2H, m), 2.05-1.10 (8H, m) Purity >90% (NMR) MS 552 (M+1)

[2064] 205 TABLE 205 Example No. 309 1HNMR(&dgr;)ppm 918 300MHz, DMSO-d6 8.33(1H, s), 8.15 and 7.99 (2H, ABq, J=8.9Hz), 7.84 and 7.59(4H, A′ B′ q, J=8.3Hz), 7.46 (2H, d, J=8.4Hz), 7.22-7.16 (3H, m), 7.01-6.98(2H, m), 4.27 and 4.23(2H, A″B″q, J=1 2.9Hz), 3.78(3H, s), 2.39-2.21(2H, brm), 2.07-1.95(2H, brm), 1.91-1.80(2H, brm), # 1.72-1.59(1H, brm), 1.49-1.17(3H, brm) Purity >90% (NMR) MS Example No. 310 1HNMR(&dgr;)ppm 919 300MHz, DMSO-d6 8.33(1H, s), 8.09 and 7.95 (2H, ABq, J=8.7Hz), 7.87 and 7.71(4H, A′ B′ q, J=8.0Hz), 7.43(2H, d, J=7.8Hz), 7.15(1H, d, J=8.7Hz), 7.07-7.02(4H, m), 4.66(2H, s), 4.23(1H, br t, J=11.8Hz), 3.76(3H, s), 2.38-2.20(2H, brm), 2.04-1.93(2H, brm), 1.89-1.79(2H, # brm), 1.70-1.59(1H, brm), 1.49-1.18(3H, brm) Purity > 90% (NMR) MS 615(M +1) Example No. 311 1HNMR(&dgr;) ppm 920 300MHz, DMSO-d6 8.30(1H, s), 8.21 and 8.01(2H, ABq, J=8.7Hz), 7.65(2H, d, J=8.4Hz), 7.52-7.41(6H, m), 7.20(1H, d, J=8.4Hz), 7.14 (1H, d, J=2.7Hz), 6.97(1H, dd, J=8.4, 2.4Hz), 4.31(1H, brt, J=9.8Hz), 4.28(2H, s), 3.78(3H, s), 2.37-2.20(2H, brm), 2.07-1.95(2H, brm), 1.92-1.80(2H, brm), 1.71- # 1.60(1H, brm), 1.50-1.19(3H, brm) MS 583(M +1)

[2065] 206 TABLE 206 Example No. 312 1HNMR(&dgr;)ppm 921 J=8300MHz, DMSO-d6 8.22(1H, s), 8.12(1H, d, J=8.4Hz), 8.00-7.84(5H, m), 7.70(4H, d, J=8.4Hz), 7.56(1H, t, J=8.6Hz),7.23(1H, d, J=12.0Hz), 7.13(1H, d, J=8.6Hz), 6.97(1H, s), 3.92(1H, m), 2.35-2.00(2H, m), 1.95-1.70(4H, m), 1.65-1.55(1H, m), 1.50-1.05(3H, m) Purity >90% (NMR) MS 609(M+1) Example No. 313 1HNMR(&dgr;)ppm 922 J=8300MHz, DMSO-d6 8.89(1H, brs), 8.63(1H, brs), 8.24(1H, s), 8.11(1H, d, J=7.8Hz), 7.99(1H, d, J=8.8Hz), 7.89(1H, d, J=9.9Hz), 7.61-7.55(4H, m), 7.43(2H, t, J=7.7Hz), 7.34(1H, t, J=7.2 Hz), 7.24(1H, d, J=12.0Hz), 7.14(1H, d, J=8.6Hz), 6.95 (1H, s), 3.96(1H, m), 2.35-2.05(2H, m), 2.00-1.50(5H, m), # 1.45-1.10(3H, m) Purity >90% (NMR) MS 522 (M+1) Example No. 314 1HNMR(&dgr;)ppm 923 J=8300MHz, CDCl3 8.48(1H, d, J=1.4Hz), 8.05 (1H, d, J=1.8Hz), 8.98(1H, d, J=8.6Hz), 7.82(1H, d, J=7.9 Hz), 7.66(1H, d, J=8.6Hz), 7.55-7.24(6H, m), 6.78(1H, dd, J=8.6, 2.6Hz), 6.69(1H, dd J=11.6Hz), 2.2Hz), 6.40-6.30(1H, m), 4.99(2H, s), 4.02(1H, m), 3.95(3H, s), 3.05 (3H, d, J=4.8Hz), 2.32-2.13 # (2H, m), 2.03-1.87(4H, m), 1.81-1.71(1H, m), 1.46-1.23 (3H, m) Purity > 90% (NMR) MS 626(M+1)

[2066] 207 TABLE 207 Example No. 503 1HNMR(&dgr;)ppm 924 300MHz, DMSO-d6 8.23(1H, s), 7.76(1H, d, J=8.7 Hz), 7.58(1H, d, J=8.8Hz), 7.51-7.32(7H, m), 7.17(2H, d, J=8.7Hz), 6.55(1H, s), 5.18(2H, s), 4.75(1H, m), 2.35 2.12(2H, m), 2.10-1.85 (4H, m), 1.80-1.50(2H, m) Purity >90% (NMR) MS 412(M+1) Example No. 701 1HNMR(&dgr;)ppm 925 300MHz, DMSO-d6 8.96(1H, s), 8.50(1H, s), 7.77(2H, d, J=8.7Hz), 7.50-7.40(4H, m), 7.30(1H, d, J=8.4 Hz), 7.24(1H, d, J=2.4Hz), 7.16(2H, d, J=8.4Hz), 7.06(1H, dd, J=2.4Hz, 8.1Hz), 5.06 (2H, s), 4.31(1H, s), 3.83(3H, s), 2.80-2.55(2H, m), 2.00-1.80(4H, m), 1.70-1.55(1H, m), 1.40-1.15(3H, m) Purity > 90% (NMR) MS 568(M+1)

[2067] 208 TABLE 208 Example No. 315 1HNMR(&dgr;) ppm 926 m)300MHz, DMSO-d6 8.84(2H, d, J=6.3Hz), 8.28(1H, s), 8.17 and 7.99(2H, ABq, J=8.7Hz), 7.87-7.85(3H, m), 7.70-7.50(3H, m), 7.52(1H, d, J=8.3 Hz), 7.18(2H, d, J=8.7Hz), 5.22(2H, s)4.31(1H, br t, J=12.5Hz), 2.36-2.18(2H, m), 2.03-1.78(4H, m), 1.70-1.58(1H, m), 1.50-1.23(3H, m) Purity >90% (NMR) MS 538 (M+1) Example No. 316 1HNMR(&dgr;) ppm 927 m)300MHz, DMSO-d6 9.23(1H, t, J=6.3Hz), 8.29(1H, s), 8.25-8.22(2H, m), 8.03(2H, d, J=7.9Hz), 7.55-7.48(5H, m) 7.34(4H, d, J=4.4Hz), 7.28-7.22 (3H, m), 5.15(2H, s), 4.52(2H, d, J=5.9Hz), 4.35(1H,br t, J=12.1Hz), 2.37-2.18(2H, m), 2.08-1.95(2H, m), 1.91-1.79 (2H, m), 1.72-1.59(1H, m), 1.47-1.19(3H, # m) Purity >90% (NMR) MS 670(M+1) Example No. 317 1HNMR(&dgr;) ppm 928 m)300MHz, DMSO-d6 8.59(1H, t, J=5.5Hz), 8.28(1H, s), 8.21 and 8.01(2H, ABq, J=8.8 Hz), 8.16(1H, s), 7.97 and 7.46 (2H, A′B′q, J=8.0Hz), 7.71 and 7.23(4H, A″B″q, J=8.7Hz), 7.53 and 7.49(4H, A″′B″′q, J=9.2Hz), 5.14(2H, s), 4.34(1H,br Hz), 2.38-2.18(2H, m), 2.07- # 1.78(4H, m), 1.78-1.47(7H, m), 1.47-1.07(6H, m), 1.03-0.83(2H, m) Purity > 90% (NMR) MS 676(M+1)

[2068] 209 TABLE 209 Example No. 318 1HNMR(&dgr;) ppm 929 300MHz, DMSO-d6 9.63 (1H, t, J=4.8Hz), 8.86 and 7.97 (4H, ABq, J=6.6Hz), 8.30(1H, s), 8.27(1H, s), 8.23 and 8.03(2H, A′B′ q, J=8.8Hz), 8.09 and 7.54 (2H, A″B″q, J=8.1Hz), 7.73 and 7.24(4H, A″′B″′q, J=8.8Hz), 7.54 and 7. 52(4H, A″″B″″q, J=8.8Hz), 5.16(2H, s)4.78(2H, d, J=5.6Hz), # 4.35(1H, br t, J=11.0Hz), 2.39-2.19(2H, m), 2.07-1.96(2H, m), 1.91-1.78 (2H, m), 1.70-1.57(1H, m)1.50-1.19(3H, m) Purity > 90% (NMR) MS 671(M+1) Example No. 319 1HNMR(&dgr;) ppm 930 300MHz, DMSO-d6 8.28(1H, s), 8.24 and 8.03(2H, A Bq, J=9.0Hz), 7.77(1H, s), 7.70 (2H, d, J=8.4Hz), 7.64-7.10 (13H, m), 5.16(2H, s), 4.74 and 4.57 (total 2H, each br s), 4.34(1H, br t, J=11.7Hz), 2.90(3H, s), 2.35-2.17(2H, m), 2.07-1.93(2H, m), 1.93-1.78(2H, m), 1.71-1.57 (1H, m), 1.51-1.19(3H, m) Purity > 90% (NMR) MS 684(M+1) Example No. 320 1HNMR(&dgr;) ppm 931 300MHz, DMSO-d6 8.94 and 8.06(4H, ABq, J=6.8Hz) 8.33(1H, s), 8.28 and 8.05(2H, A′B′q, J=8.7Hz), 7.80(1H, s), 7.73 and 7.22(4H, A″B″q, J=8.7Hz), 7.63 and 7.57(2H, A″′B″′q, J=7.9Hz), 5.30(2H, s), 4.34(1H, br t, J=12.1Hz), 3.04(3H, s), 2.97 (3H, s),2.38-2.18(2H, m), 2.10-1.96(2H, m). 1.93-1.80(2H. m), # 1.72-1.58(1H, m), 1.52-1.08 (3H, m) Purity > 90% (NMR) MS 575(M+1)

[2069] 210 TABLE 210 Example No. 321 1HNMR(&dgr;) ppm 932 H,300MHz, DMSO-d6 11.19(1H, br s), 8.31(1H, s), 8.23 and 8.02 (2H, ABq, J=9.0Hz), 7.77(1H, s), 7.72 and 7.23(4H, A′B′q, J=8.7Hz), 7.59 and 7.48(2H, A″B″q, J=7.9Hz), 7.53 and 7.51(4H, A″′B″′q, J=9.0Hz), 5.16(2H, s), 4.72-2.97(8H, br m), 4.34(1H, br t, J=12.1Hz), 2.79(3H, s), 2.38- # 2.17(2H, m), 2.07-1.93(2H,m), 1.93-1.78(2H, m), 1.69-1.58 (1H, m), 1.50-1.10(3H, m) Purity > 90% (NMR) MS 663 (M+1) Example No. 322 1 NMR(&dgr;) ppm 933 H,300MHz, DMSO-d6 9.64(1H, t, J=5.7Hz), 8.91(1H, s), 8.81(1H, d, J=4.9Hz), 8.48(1H, d, J=7.9Hz), 8.32(1H, s), 8.27(1H, d, J=9.0Hz), 8.25(1H, s), 8.07-7.97(3H, m), 7.74 and 7.25 (4H, ABq, J=8.9Hz), 7.56-7.49 (5H, m) , 5.16(2H, s), 4.69(2H, d, J=5.6Hz), 4.36(1H, br t, J=12.4Hz), 2.37-2.20(2H, m), 2.09-1.97(2H, m), 1.91-1.78 # 2H, m) , 1.70-1.57(1H, m), 1.50-1.17(3H, m) Purity >90% (NMR) MS 671 (M+1) Example No. 323 1HNMR(&dgr;) ppm 934 H,300MHz, DMSO-d6 9.52(1H, t, J=6.0Hz), 8.72(1H, d, J=5.3Hz), 8.30-8.19(4H, m), 8. 08(1H, d, J7. 9Hz), 8. 02 (1H, d, J=7.6HZ), 7.77-7.64(4H, m), 7.57-7.49(5H, m), 7.24(2H, d, J=8.7Hz), 5.16(2H, s), 4.77(2H, d, J=5.6Hz), 4.34(1H, t, J=12.8 Hz), 2.36-2.19(2H, m), 2.07-1.95(2H, m), 1.91-1.78(2H, m), #1.69-1.59(1H, m), 1.45-1.20(3H, m) Purity >90% (NMR) MS 671 (M+1)

[2070] 211 TABLE 211 Example No. 324 1HNMR(&dgr;) ppm 935 300MHz, DMSO-d6 8.36(1H, d, J=7.9Hz), 8.30(1H, s), 8.28 and 8.05(2H, ABq, J=8.8Hz), 8.16(1H, s),7.79 and 7.46 (2H, A′B′q, J=8.3Hz), 7.74 and 7.25(4H, A″B″q, J=8.9Hz), 7.52 and 7.50(4H, A″′B″′q, J=8.7Hz), 5.14(2H, s), 4.36(1H, br t, J=12.1Hz), 3.80(1H, br s), 2.39-2.18(2H, m), 2.10- #1.98(2H, m), 1.93-1.57(8H, m), 1.49-1.04(8H, m) Purity >90% (NMR). MS 662(M+1) Example No. 325 1HNMR(&dgr;) ppm 936 300MHz, DMSO-d6 8.86(1H, t, J=6.0Hz), 8.84 and 8.00(4H, ABq, J=6.6Hz), 8.33(1H, s), 8.27 and 8.04(2H, A′B′q, J=9.0Hz), 8.12(1H, s), 7.92 and 7.46 (2H, A″B″q, J=7.9Hz), 7.74 and 7.23(4H, A″′B″′q, J=9.0Hz), 7.53 and 7.49(4H, A″″B″″q, J=9.1 Hz), 5.13(2H, s), 4.36(1H, br t, J=12.8Hz), 3.70(2H, td, J= #6.0Hz), 3.21(2H, t, J=6.8Hz), 2.38-2.20(2H, m), 2.09-1.95 (2H, m), 1.91-1.77(2H, m), 1.70-1.59(1H, m), 1.49-1.20(3H, m) Purity >90% (NMR) MS 685(M+1) Example No. 326 1HNMR(&dgr;) ppm 937 300MHz, DMSO-d6 12.80(1H, brs), 8.23(1H, s), 7.90(1H, d, J=8.7Hz), 7.83(1H, d, J=8.7Hz), 7.60-7.50(5H, m), 7.39(2H, d, J=7.8Hz), 7.23-7.10 (3H, m), 7.05(1H, d, J=7.8Hz), 6.85(1H, s), 3.94(1H, s), 2.97, 2.88(6H, s), 2.30-2.10(2H, m), 1.90-1.50(5H, m), 1.40-1.00(3H, m) Purity >90% (NMR) MS 610(M+1)

[2071] 212 TABLE 212 Example No. 327 1HNMR(&dgr;) ppm 938 H,300MHz, DMSO-d6 13.20-12.60(2H, brs), 8.23(1H, s), 7.98(2H, d, J=6.6Hz), 7.95 (1H, d, J=8.7Hz), 7.87(1H, d, J=8.7Hz), 7.70-7.50(5H, m), 7.27-7.20(3H, m), 7.08(1H, d, J=7 8 Hz), 6.90(1H, s), 3.93(1H, s), 2.51-2.05(2H, m), 1.90-1.70(4H, m), 1.65-1.55(1H, m), 1.40-1.10(3H, m) Purity >90% (NMR) MS 583(M+1)

[2072] 213 TABLE 213 939 Ex. No. R R′ 2001 —H 4-(-Me) 2002 —H 3-(—CF3) 2003 5-(—F) —H 2004 3-(—F) 2-(—F) 2005 3-(—F) 3-(—F) 2006 3-(—F) 4-(—F) 2007 4-(—F) 4-(—F) 2008 5-(—F) 4-(—F) 2009 6-(—F) 4-(—F) 2010 4-(—F) 4-(—Cl) 2011 5-(—F) 4-(—Me) 2012 5-(—F) 4-(—CF3) 2013 5-(—F) 4-(—CO2H) 2014 5-(—F) 4-(—CO2Me) 2015 5-(—F) 940 2016 5-(—F) 4-(—CONH2) 2017 5-(—F) 4-{—CON(Me)2} 2018 5-(—F) 4-(—OMe) 2019 5-(—F) 4-(—SMe) 2020 5-(—F) 941 2021 5-(—F) 942 2022 4-(—Cl) —H 2023 4-(—Cl) 4-(—F) 2024 4-(—Cl) 4-(—Cl) 2025 4-(—Cl) 4-(—Me) 2026 5-(—Cl) 4-(—CF3) 2027 4-(—Cl) 4-(—CO2H) 2028 5-(—Cl) 4-(—CO2Me) 2029 5-(—Cl) 943 2030 4-(—Cl) 4-(—CONH2) 2031 5-(—Cl) 4-{—CON(Me)2} 2032 5-(—Cl) 3-(—OMe) 2033 4-(—Cl) 4-(—SMe) 2034 5-(—Cl) 944 2035 4-(Cl) 945 2036 5-(—CN) 4-(—F) 2037 4-(—CN) 4-(—Cl) 2038 5-(—NO2) 4-(—F) 2039 4-(—NO2) 4-(—Cl) 2040 5-(—Me) 4-(—CO2H) 2041 5-(—Me) 4-(—CO2Me) 2042 5-(—Me) 946 2043 5-(—CF3) 4-(—CO2H) 2044 5-(—CF3) 4-(—CO2Me) 2045 5-(—CF3) 947 2046 5-(—CO2H) 4-(—F) 2047 4-(—CO2H) 4-(—Cl) 2048 5-(—CO2Me) 4-(—F) 2049 5-(—CO2Me) 4-(—Cl) 2050 5-(—Ac) 4-(—F) 2051 5-(—Ac) 4-(—Cl) 2052 948 —H 2053 949 4-(—F) 2054 950 4-(—Cl) 2055 951 4-(—CN) 2056 952 4-(—NO2) 2057 953 4-(—Me) 2058 954 4-(—CF3) 2059 955 4-(—Ac) 2060 956 4-(—CO2H) 2061 957 4-(—CO2Me) 2063 958 4-(—CONH2) 2064 959 4-{—CON(Me)2} 2065 960 4-{—C(═NH)NH2} 2066 961 4-(—OMe) 2067 962 963 2068 964 4-(—NHMe) 2069 965 4-(—NHAc) 2070 966 967 2071 968 4-(—SMe) 2072 969 970 2073 971 972 2074 973 974 2075 975 976 2076 5-(—CONH2) —H 2077 5-(—CONH2) 4-(—F) 2078 5-(—CONH2) 2,3,4,5,6-penta-(—F) 2079 5-(—CONH2) 2-(—Cl) 2080 5-(—CONH2) 3-(—Cl) 2081 3-(—CONH2) 2-(—Cl) 2082 3-(—CONH2) 3-(—Cl) 2083 3-(—CONH2) 4-(—Cl) 2084 4-(—CONH2) 2-(—CI) 2085 4-(—CONH2) 3-(—Cl) 2086 4-(—CONH2) 4-(—Cl) 2087 6-(—CONH2) 2-(—Cl) 2088 6-(—CONH2) 3-(—Cl) 2089 6-(—CONH2) 4-(—Cl) 2090 5-CONH2) 3,5-di-(—Cl) 2091 5-(—CONH2) 4-(—CN) 2092 5-(—CONH2) 4-(—NO2) 2093 5-(—CONH2) 4-(—Me) 2094 5-(—CONH2) 2,6-di-(—Me) 2095 5-(—CONH2) 4-(—CF3) 2096 5-(—CONH2) 4-(—Ac) 2097 5-(—CONH2) 4-(—CO2H) 2098 5-(—CONH2) 4-(—CO2Me) 2099 5-(—CONH2) 977 2100 5-(—CONH2) 4-(—CONH2) 2101 5-(—CONH2) 3,5-di-(—CONH2) 2102 5-(—CONH2) 4-{—CON(Me)2} 2103 5-(—CONH2) 4-{—C(═NH)NH2} 2104 5-(—CONH2) 4-(—OMe) 2105 5-(—CONH2) 3,4,5-tri-(—OMe) 2106 5-(—CONH2) 978 2107 5-(—CONH2) 4-(—NHMe) 2108 5-(—CONH2) 4-(—NHAc) 2109 5-(—CONH2) 979 2110 5-(—CONH2) 4-(—SMe) 2111 5-(—CONH2) 980 2112 5-(—CONH2) 981 2113 5-(—CONH2) 982 2114 5-(—CONH2) 983 2115 5-{—CON(Me)2} —H 2116 5-{—CON(Me)2} 4-(—F) 2117 4-{—CON(Me)2} 4-(—Cl) 2118 5-{—CON(Me)2} 4-(—CN) 2119 5-{CON(Me)2} 4-(—NO2) 2120 5-{—CON(Me)2} 4-(—Me) 2121 4-{—CON(Me)2} 4-(—CF3) 2122 5-{—CON(Me)2} 4-(—Ac) 2123 5-{—CON(Me)2} 4-(—CO2H) 2124 5-{—CON(Me)hd 2} 4-(—CO2Me) 2125 5-{—CON(Me)2} 984 2126 5-{—CON(Me)2} 3-(—CONH2) 2127 4-({—CON(Me)2} 4-{—CON(Me)2} 2128 5-{—CON(Me)2} 4-{—C(═NH)NH2} 2129 5-{—CON(Me)2} 4-(—OMe) 2130 5-{—CON(Me)2{ 985 2131 5-{—CON(Me)2} 4-(—NHMe) 2132 5-{CON(Me)2} 4-(—NHAc) 2133 5-{—CON(Me)2} 986 2134 4-{—CON(Me)2} 4-(—SMe) 2135 5-{—CON(Me)2} 987 2136 4-{—CON(Me)2} 988 2137 5-{-CON(Me)2} 989 2138 5-{-CON(Me)2} 990 2139 5-(—OMe) —H 2140 5-(—OMe) 4-(—F) 2141 3-(—OMe) 4-(—Cl) 2142 4-(OMe) 4-(—Cl) 2143 5-(—OMe) 2-(—Cl) 2144 5-(—OMe) 3-(—Cl) 2145 6-(—OMe) 4-(—Cl) 2146 5-(—OMe) 4-(—CN) 2147 5-(—OMe) 4-(—NO2) 2148 5-(—OMe) 4-(—Me) 2149 5-(—OMe) 4-(—CF3) 2150 5-(—OMe) 4-(—Ac) 2151 4-(—OMe) 4-(—CO2H) 2152 4,5-di-(—OMe) 4-(—CO2H) 2153 5-(—OMe) 4-(—CO2Me) 2154 5-(—OMe) 991 2155 5-(—OMe) 4-(—CONH2) 2156 5-(—OMe) 4-{—CON(Me)2} 2157 5-(—OMe) 4-{—C(═NH)NH2} 2158 5-(—OMe) 4-(—OMe) 2159 5-(—OMe) 992 2160 5-(—OMe) 4-(—NHMe) 2161 5-(—OMe) 4-(—NHAc) 2162 5-(—OMe) 993 2163 5-(—OMe) 4-(—SMe) 2164 5-(—OMe) 994 2165 5-(—OMe) 995 2166 5-(—OMe) 996 2167 5-(—OMe) 997 2168 5-(—NHMe) 4-(—F) 2169 5-(—NHMe) 4-(—Cl) 2170 5-(—NHAc) 4-(—F) 2171 5-(—NHAc) 4-(—Cl) 2172 5-(—NHAc) 4-(—Ac) 2173 5-(—NHAc) 4-(—CONH2) 2174 5-(—NHAc) 4-{—CON(Me)2} 2175 998 4-(—F) 2176 999 4-(—Cl) 2177 1000 4-(—Me) 2178 1001 4-(—CF3) 2179 1002 4-(—CO2H) 2180 1003 4-(—CO2Me) 2181 1004 1005 2182 1006 4-(—SMe) 2183 1007 1008 2184 1009 1010 2185 5-(—SMe) 4-(—F) 2186 4-(—SMe) 4-(—Cl) 2187 5-(—SMe) 4-(—Me) 2188 5-(—SMe) 4-(—CF3) 2189 5-(—SMe) 4-(—Ac) 2190 5-(—SMe) 4-(—CONH2) 2191 5-(—SMe) 4-{—CON(Me)2} 2192 1011 4-(—F) 2193 1012 4-(—Cl) 2194 1013 4-(—Me) 2195 1014 4-(—CF3) 2196 1015 4-(—Ac) 2197 1016 4-(—CONH2) 2198 1017 4-{—CON(Me)2} 2199 1018 4-(—F) 2200 1019 4-(—Cl) 2201 1020 4-(—Me) 2202 1021 4-(—CF3) 2203 1022 4-(—Ac) 2204 1023 4-(—CONH2) 2205 1024 4-{—CON(Me)2} 2206 1025 4-(—F) 2207 1026 4-(—Cl) 2208 1027 2,4-di(—Cl) 2209 1028 4-(—Me) 2210 1029 3-(—CF3) 2211 1030 4-(—CF3) 2212 1031 4-(—CONH2) 2213 1032 4-{—CON(Me)2} 2214 1033 4-(—SMe) 2215 1034 1035 2216 1036 1037 2217 1038 4-(—F) 2218 1039 4-(—Cl) 2219 1040 4-(—Me) 2220 1041 4-(—CF3) 2221 1042 4-(—CONH2) 2222 1043 4-{—CON(Me)2} 2223 1044 4-(—SMe) 2224 1045 1046 2225 1047 1048 2226 5-{—O—(CH2)2—OH} 4-(—Cl) 2227 5-{—O—(CH2)3—OH} 4-(—Cl) 2229 1049 4-(—Cl) 2230 1050 4-(—Cl) 2231 1051 4-(—Cl) 2232 1052 4-(—Cl) 2233 1053 4-(—Cl) 2234 1054 4-(—Cl) 2235 1055 4-(—Cl) 2236 1056 4-(—Cl) 2237 1057 4-(—Cl) 2238 1058 4-(—Cl) 2239 1059 4-(—Cl) 2240 1060 4-(—Cl) 2241 1061 4-(—Cl) 2242 1062 4-(—Cl) 2243 1063 4-(—Cl) 2244 1064 4-(—Cl) 2245 1065 4-(—Cl) 2246 1066 4-(—Cl) 2247 1067 4-(—Cl) 2248 1068 4-(—Cl) 2249 1069 4-(—Cl) 2250 1070 4-(—Cl) 2251 1071 4-(—Cl) 2252 1072 4-(—Cl) 2253 1073 4-(—Cl) 2254 1074 4-(—Cl)

[2073] 214 TABLE 214 1075 Ex. No. R R′ 2255 —H —H 2256 —H 4-(—Me) 2257 —H 3-(—CF3) 2258 5-(—F) —H 2259 5-(—F) 4-(—F) 2260 5-(—F) 4-(—Cl) 2261 5-(—F) 4-(—Me) 2262 5-(—F) 4-(—CF3) 2263 5-(—F) 4-(—CO2H) 2264 5-(—F) 4-(—CO2Me) 2265 5-(—F) 1076 2266 5-(—F) 4-(—CONH2) 2267 5-(—F) 4-{—CON(Me)2} 2268 5-(—F) 4-(—OMe) 2269 5-(—F) 4-(—SMe) 2270 5-(—F) 1077 2271 5-(—F) 1078 2272 4-(—Cl) —H 2273 5-(—Cl) 4-(—F) 2274 4-(—Cl) 4-(—Cl) 2275 5-(—Cl) 4-(—Me) 2276 5-(—Cl) 4-(—CF3) 2277 5-(—Cl) 4-(—CO2H) 2278 5-(—Cl) 4-(—CO2Me) 2279 5-(—Cl) 1079 2280 5-(—Cl) 4-(—CONH2) 2281 5-(—Cl) 4-{—CON(Me)2} 2282 5-(—Cl) 4-(—OMe) 2283 5-(—Cl) 4-(—SMe) 2284 5-(—Cl) 1080 2285 5-(—Cl) 1081 2286 5-(—Cl) 4-(—F) 2287 5-(—Cl) 4-(—Cl) 2288 5-(—NO2) 4-(—F) 2289 5-(—NO2) 4-(—Cl) 2290 5-(—Me) 4-(—CO2H) 2291 5-(—Me) 4-(—CO2Me) 2292 5-(—Me) 1082 2293 5-(—CF3) 4-(—CO2H) 2294 5-(CF3) 4-(—CO2Me) 2295 5-(—CF3) 1083 2296 5-(—CO2H) 4-(—F) 2297 4-(—CO2H) 4-(—Cl) 2298 5-(—CO2Me) 4-(—F) 2299 5-(—CO2Me) 4-(—Cl) 2300 5-(—Ac) 4-(—F) 2301 5-(—Ac) 4-(—Cl) 2302 1084 —H 2303 1085 4-(—F) 2304 1086 4-(—Cl) 2305 1087 4-(—CN) 2306 1088 4-(—NO2) 2307 1089 4-(—Me) 2308 1090 4-(—CF3) 2309 1091 4-(—Ac) 2310 1092 4-(—CO2H) 2311 1093 4-(—CO2Me) 2312 1094 1095 2313 1096 4-(—CONH2) 2314 1097 4-{{—CON(Me)256 2315 1098 4-{—C(═NH)NH2} 2316 1099 4-(—OMe) 2317 1100 1101 2318 1102 4-(—NHMe) 2319 1103 4-(—NHAc) 2320 1104 1105 2321 1106 4-(—SMe) 2322 1107 1108 2323 1109 1110 2324 1111 1112 2325 1113 1114 2326 5-(—CONH2) —H 2327 5-(—CONH2) 4-(—F) 2328 5-(—CONH2) 4-(—Cl) 2329 5-(—CONH2) 4-(—CN) 2330 5-(—CONH2) 4-(—NO2) 2331 5-(—CONH2) 4-(—Me) 2332 5-(—CONH2) 4-(—CF3) 2333 5-(—CONH2) 4-(—Ac) 2334 5-(—CONH2) 4-(—CO2H) 2335 5-(—CONH2) 4-(—CO2Me) 2336 5-(—CONH2) 1115 2337 5-(—CONH2) 4-(—CONH2) 2338 5-(—CONH2) 4-{—CON(Me)2} 2339 5-(—CONH2) 4-{—C(═NH)NH2} 2340 5-(—CONH2) 4-(—OMe) 2341 5-(—CONH2) 1116 2342 5-(—CONH2) 4-(—NHMe) 2343 5-(—CONH2) 4-(—NHAc) 2344 5-(—CONH2) 1117 2345 5-(—CONH2) 4-(—SMe) 2346 5-(—CONH2) 1118 2347 5-(—CONH2) 1119 2348 5-(—CONH2) 1120 2349 5-(—CONH2) 1121 2350 5-{—CON(Me)2} —H 2351 5-{—CON(Me)2} 4-(—F) 2352 4-{—CON(Me)2} 4-(Cl) 2353 5-{—CON(Me)2} 4-(—CN) 2354 5-{—CON(Me)2} 4-(—NO2) 2355 5-{—CON(Me)2} 4-(—Me) 2356 5-{—CON(Me)2} 4-(—CF3) 2357 5-{—CON(Me)2} 4-(—Ac) 2358 5-{—CON(Me)2} 4-(—CO2H) 2359 5-{—CON(Me)2} 4-(—CO2Me) 2360 5-(—CON(Me)2} 1122 2361 5-{—CON(Me)2} 4-(—CONH2) 2362 5-{—CON(Me)2} 4-{—CON(Me)2} 2363 5-{—CON(Me)2} 4-{—C(═NH)NH2} 2364 5-{—CON(Me)2} 4-(—OMe) 2365 5-{—CON(Me)2} 1123 2366 5-{—CON(Me)2} 4-(—NHMe) 2367 5-{—CON(Me)2} 4-(—NHAc) 2368 5-{—CON(Me)2} 1124 2369 5-{—CON(Me)2} 4-(—SMe) 2370 5-{—CON(Me)2} 1125 2371 5-{—CON(Me)2} 1126 2372 5-{—CON(Me)2} 1127 2373 5{CON(Me)2} 1128 2374 5-(—OMe) —H 2375 5-(—OMe) 4-(—F) 2376 5-(—OMe) 4-(—Cl) 2377 5-(—OMe) 4-(—CN) 2378 5-(—OMe) 4-(—NO2) 2379 5-(—OMe) 4-(—Me) 2380 5-(—OMe) 4-(—CF3) 2381 5-(—OMe) 4-(—Ac) 2382 5-(—OMe) 4-(—CO2H) 2383 5-(—OMe) 4-(—CO2Me) 2384 5-(—OMe) 1129 2385 5-(—OMe) 4-(—CONH2) 2386 5-(—OMe) 4-{—CON(Me)2} 2387 5-(—OMe) 4-{—C(═NH)NH2} 2388 5-(—OMe) 4-(—OMe) 2389 5-(—OMe) 1130 2390 5-(—OMe) 4-(—NHMe) 2391 5-(—OMe) 4-(—NHAc) 2392 5-(—OMe) 1131 2393 5-(—OMe) 4-(—SMe) 2394 5-(—OMe) 1132 2395 5-(—OMe) 1133 2396 5-(—OMe) 1134 2397 5-(—OMe) 1135 2398 5-(—NHMe) 4-(—F) 2399 5-(—NHMe) 4-(—Cl) 2400 5-(—NHAc) 4-(—F) 2401 5-(—NHAc) 4-(—Cl) 2402 5-(—NHAc) 4-(—Ac) 2403 5-(—NHAc) 4-(—CONH2) 2404 5-(—NHAc) 4-{—CON(Me)2} 2405 1136 4-(—F) 2406 1137 4-(—Cl) 2407 1138 4-(—Me) 2408 1139 4-(—CF3) 2409 1140 4-(—CO2H) 2410 1141 4-(—CO2Me) 2411 1142 1143 2412 1144 4-(—SMe) 2413 1145 1146 2414 1147 1148 2415 5-(—SMe) 4-(—F) 2416 5-(—SMe) 4-(—Cl) 2417 5-(—SMe) 4-(—Me) 2418 5-(—SMe) 4-(—CF3) 2419 5-(—SMe) 4-(—Ac) 2420 5-(—SMe) 4-(—CONH2) 2421 5-(—SMe) 4-{—CON(Me)2} 2422 1149 4-(—F) 2423 1150 4-(—Cl) 2424 1151 4-(—Me) 2426 1152 4-(—Ac) 2427 1153 4-(—CONH2) 2428 1154 4-{—CON(Me)2} 2429 1155 4-(—F) 2430 1156 4-(—Cl) 2431 1157 4-(—Me) 2432 1158 4-(—CF3) 2433 1159 4-(—Ac) 2434 1160 4-(—CONH2) 2435 1161 4-{—CON(Me)2} 2436 1162 4-(—F) 2437 1163 4-(—Cl) 2438 1164 4-(—Me) 2439 1165 4-(—CF3) 2440 1166 4-(—CONH2) 2441 1167 4-{-CON(Me)2} 2442 1168 4-(—SMe) 2443 1169 1170 2444 1171 1172 2445 1173 4-(—F) 2446 1174 4-(—Cl) 2447 1175 4-(—Me) 2448 1176 4-(—CF3) 2449 1177 4-(—CONH2) 2450 1178 4-{—CON(Me)2} 2451 1179 4-(—SMe) 2452 1180 1181 2453 1182 1183

[2074] 215 TABLE 215 1184 Ex. No. R R′ 2454 2-(—F) 2-(—F) 2455 2-(—F) 3-(—F) 2456 2-(—F) 4-(—F) 2457 3-(—Cl) 3-(—Cl) 2458 3,5-di-(—Cl) 3,5-di-(—Cl) 2459 3-(—CN) 3-(—CN) 2460 3-(—NO2) 3-(—NO2) 2461 3-(—Me) 3-(—Me) 2462 3-(—CF3) 3-(—CF3) 2463 3-(—Ac) 3-(—Ac) 2464 3-(—CO2H) 3-(—CO2H) 2465 3-(—CO2Me) 3-(—CO2Me) 2466 1185 1186 2467 3-(—CONH2) 3-(—CONH2) 2468 3-(—CONH2) 3-(—F) 2469 3-(—CONH2) 3-(—Cl) 2470 3-(—CON(Me)2} 3-{-CON(Me)2} 2471 3-{—CON(Me)2} 3-(—F) 2472 3-(—CON(Me)2} 3-(—Cl) 2473 3-{—C(═NH)NH2} 3-{—C(═NH)NH2} 2474 3-(—OMe) 3-(—OMe) 2475 1187 1188 2476 3-(—NHMe) 3-(—NHMe) 2477 3-(—NHAc) 3-(—NHAc) 2478 1189 1190 2479 3-(—SMe) 3-(—SMe) 2480 1191 1192 2481 1193 1194 2482 1195 1196 2483 1197 1198 2484 3-(—F) 4-(—F) 2485 3-(—Cl) 4-(—Cl) 2486 4-(—CN) 4-(—CN) 2487 4-(—NO2) 4-(—NO2) 2488 3-(—Me) 4-(—Me) 2489 4-(—Me) 2,6-di-(—Me) 2490 4-(—CF3) 4-(—CF3) 2491 4-(—Ac) 4-(—Ac) 2492 4-(—CO2H) 4-(—CO2H) 2493 4-(—CO2Me) 4-(—CO2Me) 2494 1199 1200 2495 4-(—CONH2) 4-(—CONH2) 2496 4-(—CONH2) 4-(—F) 2497 4-(—CONH2) 2,3,4,5,6-penta-(—F) 2498 4-(—CONH2) 4-(—Cl) 2499 4-{—CON(Me)2} 4-{—CON(Me)2} 2500 4-{—CON(Me)2} 4-(—F) 2501 4-{—CON(Me)2} 4-(—Cl) 2502 4-{—CON(Me)2} 3,5-di-(—Cl) 2503 4-{—C(═NH)NH2} 4-{—C(═NH)NH2} 2504 4-(—OMe) 4-(—OMe) 2505 4-(—OMe) 3,4,5-tri-(—OMe) 2506 1201 1202 2507 4-(—NHMe) 4-(—NHMe) 2508 4-(—NHAc) 4-(—NHAc) 2509 1203 1204 2510 4-(—SMe) 4-(—SMe) 2511 1205 1206 2512 1207 1208 2513 1209 1210 2514 1211 1212

[2075] 216 TABLE 216 1213 Ex. No. R R′ 2515 —H —H 2516 2-(—F) 3-(—F) 2517 3-(—Cl) 3-(—Cl) 2518 3-(—CN) 3-(—CN) 2519 3-(—NO2) 3-(—NO2) 2520 3-(—Me) 3-(—Me) 2521 3-(—CF3) 3-(—CF3) 2522 3-(—Ac) 3-(—Ac) 2523 3-(—CO2H) 3-(—CO2H) 2524 3-(—CO2Me) 3-(—CO2Me) 2525 1214 1215 2526 3-(—CONH2) 3-(—CONH2) 2527 3-(—CONH2) 3-(—F) 2528 3-(—CONH2) 3-(—Cl) 2529 3-{—CON(Me)2} 3-{—CON(Me)2} 2530 3-{—CON(Me)2} 3-(—F) 2531 3-{—CON(Me)2} 3-(—Cl) 2532 3-(—C(═NH)NH2} 3-{—C(═NH)NH2} 2533 3-(—OMe) 3-(—OMe) 2534 1216 1217 2535 3-(—NHMe) 3-(—NHMe) 2536 3-(—NHAc) 3-(—NHAc) 2537 1218 1219 2538 3-(—SMe) 3-(—SMe) 2539 1220 1221 2540 1222 1223 2541 1224 1225 2542 1226 1227 2543 3-(—F) 4-(—F) 2544 4-(—Cl) 4-(—Cl) 2545 4-(—CN) 4-(—CN) 2546 4-(—NO2) 4-(—NO2) 2547 4-(—Me) 4-(—Me) 2548 4-(—CF3) 4-(—CF3) 2549 4-(—Ac) 4-(—Ac) 2550 3-(—CO2H) 4-(—CO2H) 2551 4-(—CO2Me) 4-(—CO2Me) 2552 1228 1229 2553 4(—CONH2) 4-(—CONH2) 2554 4-(—CONH2) 4-(—F) 2555 4-(—CONH2) 4-(—Cl) 2556 3-{—CON(Me)2} 4-{—CON(Me)2} 2557 3-{—CON(Me)2} 4-(—F) 2558 4-{—CON(Me)2} 4-(—Cl) 2559 4-{—C(═NH)NH2} 4-{{C(═NH)NH2} 2560 4-{—OMe) 4-(—OMe) 2561 1230 1231 2562 4-(—NHMe) 4-(—NHMe) 2563 4-(—NHAc) 4-(—NHAc) 2564 1232 1233 2565 4-(—SMe) 4-(—SMe) 2566 1234 1235 2567 1236 1237 2568 1238 1239 2569 1240 1241

[2076] 217 TABLE 217 1242 Ex. No. Py R′ 2570 3-Py —H 2571 3-Py 3-(—F) 2572 3-Py 3-(—Cl) 2573 3-Py 3-(—Me) 2574 3-Py 3-(—CF3) 2575 3-Py 3-(—Ac) 2576 3-Py 3-(—CO2H) 2577 3-Py 3-(—CO2Me) 2578 3-Py 1243 2579 3-Py 3-(—CONH2) 2580 3-Py 3-{—CON(Me)2} 2581 3-Py 4-(—F) 2582 3-Py 4-(—Cl) 2583 3-Py 4-(—Me) 2584 3-Py 4-(—CF3) 2585 3-Py 4-(—Ac) 2586 2-Py 4-(—CO2H) 2587 3-Py 4-(—CO2Me) 2588 3-Py 1244 2589 4-Py 4-(—CONH2) 2590 3-Py 4-{—CON(Me)2}

[2077] 218 TABLE 218 1245 Py: pyridyl group Ex. No. Py R′ 2591 3-Py —H 2592 3-Py 3-(—F) 2593 3-Py 3-(—Cl) 2594 3-Py 3-(—Me) 2595 3-Py 3-(—CF3) 2596 3-Py 3-(—Ac) 2597 3-Py 3-(—CO2H) 2598 3-Py 3-(—CO2Me) 2599 3-Py 1246 2600 3-Py 3-(—CONH2) 2601 3-Py 3-{—CON(Me)2} 2602 3-Py 4-(—F) 2603 3-Py 4-(—Cl) 2604 3-Py 4-(—Me) 2605 3-Py 4-(—CF3) 2606 3-Py 4-(—Ac) 2607 3-Py 4-(—CO2H) 2608 3-Py 4-(—CO2Me) 2609 3-Py 1247 2610 3-Py 4-(—CONH2) 2611 3-Py 4-{—CON(Me)2}

[2078] 219 TABLE 219 Example No. 328 1H NMR(&dgr;) ppm 1248 300MHz, DMSO-d6 8.29(1H, s), 8.23(1H, d, J=9.0Hz), 8.02(1H, d, J=8.4Hz), 7.80(1H, s), 7.71(2H, d, J=8.4Hz), # 7.61(1H, d, J=9.3Hz), 7.55-7.45(3H, m), 7.46(2H, d, J=8.1Hz), 7.22(2H, d, J=8.7Hz), 5.16(2H, s,), 4.34(1H, m), 4.20-3.40(4H, m), 2.60-2.15(6H, m), 2.10-1.90(2H, m), 1.85-1.70(2H, m), 1.65-1.55(1H, m), 1.50-1.10(3H, m) Purity >90% (NMR) MS 662(M + 1) Example No. 329 1H NMR(&dgr;) ppm 1249 400MHz, DMSO-d6 9.80(1H, brs), 8.32(1H, s), 8.30(1H, d, J=8.8Hz), 8.06(1H, d, J=8.8Hz), 7.74(2H, d, # J=8.6Hz), 7.48-7.37(4H, m), 7.22(1H, d, J=8.6Hz), 7.17(1H, d, J=8.2Hz), 7.05(1H, d, J=2.3Hz), 6.88(1H, dd, J=8.3, 2.5Hz), 5.04(2H, s), 4.37(1H, m), 2.37-2.22(2H, m), 2.11-1.98(2H, m), 1.93-1.81(2H, m), 1.70-1.58(1H, m), 1.56-1.22(3H, m) Purity >90% (NMR) MS 553(M + 1) Example No. 330 1H NMR(&dgr;) ppm 1250 300MHz, DMSO-d6 8.38(1H, d, J=7.5Hz), 8.32(1H, s), 8.29(1H, d, J=9.0Hz), 8.16(1H, s), 8.05(1H, d, J=9.0Hz), 7.96(1H, d, J=7.5Hz), 7.75(2H, d, J=8.4Hz), 7.53-7.43(5H, # m), 7.25(2H, d, J=8.4Hz), 5.13(2H, s), 4.36(1H, m), 4.12(1H, sept, J=6.9Hz), 2.40-2.15(2H, m), 2.10-1.95(2H, m), 1.90-1.75(2H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m), 1.18(6H, d, J=6.6Hz) Purity >90% (NMR) MS 622(M + 1)

[2079] 220 TABLE 220 Example No. 331 1H NMR(&dgr;) ppm 1251 300MHz, DMSO-d6 8.31(1H, s), 8.27(1H, d, J=8.7Hz), 8.05(1H, d, J=8.7Hz), 7.75-7.41(9H, m), 7.23(2H, d, J=8.7Hz), 4.36(1H, m), 4.00-3.90(1H, m), 2.84(3H, brs), 2.40-2.15(2H, m), 2.10-2.00(2H, m), 1.95-1.75(2H, m), 1.70-1.55(1H, m), 1.50-1.00(7H, m) Purity >90% (NMR) MS 636(M + 1) Example No. 332 1H NMR(&dgr;) ppm 1252 300MHz, DMSO-d6 10.42(1H, s), 8.29(1H, s), 8.27(1H, s), 8.10(1H, d, J=7.9Hz), 8.03(1H, d, J=8.6Hz), 7.82(2H, d, J=7.5Hz), 7.73(2H, d, J=8.7Hz), 7.56-7.52(5H, # m), 7.38(2H, t, J=7.9Hz), 7.26(2H, d, J=8.7Hz), 7.13(1H, t, J=7.5Hz), 5.20(2H, s), 4.35(1H, brt, J=11.7Hz), 2.37-2.19(2H, m), 2.07-1.96(2H, m), 1.92-1.79(2H, m), 1.69-1.58(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 656(M + 1) Example No. 333 1H NMR(&dgr;) ppm 1253 300MHz, DMSO-d6 8.30(1H, s), 8.24 and 8.03(2H, ABq, J=8.8Hz), 7.71 and 7.22(4H, A′ B′ q, J-8.8Hz), 7.69(1H, # s), 7.52(4H, s), 7.50 and 7.43(2H, A″ B″ q, J=7.7Hz), 5.15(2H, s) 4.35(1H, brt, J=12.1Hz), 4.05-3.15(5H, brm), 3.27(3H, s), 2.39-2.20(2H, m), 2.07-1.75(6H, m), 1.70-1.58(1H, m) 1.55-1.20(5H, m). Purity >90% (NMR) MS 678(M + 1)

[2080] 221 TABLE 221 Example No. 334 1H NMR(&dgr;) ppm 1254 300MHz, DMSO-d6 8.22(1H, d, J=1.5Hz), 8.01(1H, d, J=9.0Hz), 7.89(1H, dd, J=8.6, 1.5Hz), 7.61(2H, d, J=8.6Hz), 7.50-7.39(4H, # m), 7.27(1H, d, J=8.6Hz), 7.22(1H, d, J=2.6Hz), 7.13(2H, d, J=8.6Hz), 7.04(1H, dd, J=8.2, 2.6Hz), 5.04(2H, s), 4.28(1H, m), 4.11(2H, t, J=6.3Hz), 3.57(2H, t, J=6.3Hz), 2.38-2.17(2H, m), 2.00-1.79(6H, m), 1.70-1.59(1H, m), 1.52-1.16(3H, m) Purity >90% (NMR) MS 611(M + 1) Example No. 335 1H NMR(&dgr;) ppm 1255 300MHz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.27(1H, d, J=9.0Hz), 8.04(1H, dd, J=8.6, 1.5Hz), 7.72(2H, d, J=9.0Hz), 7.60-7.40(4H, # m), 7.32-7.19(4H, m), 7.06(1H, dd, J=8.6, 3.0Hz), 5.08(2H, s), 4.36(1H, m), 4.06(2H, t, J=4.8Hz), 3.74(2H, t, J=4.8Hz), 2.38-2.19(2H, m), 2.13-1.97(2H, m), 1.94-1.78(2H, m), 1.72-1.59(1H, m), 1.52-1.20(3H, m) Purity >90% (NMR) MS 597(M + 1)

[2081] 222 TABLE 222 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 340 0.017 360 0.014 341 0.025 361 0.028 342 0.015 362 0.020 343 0.017 363 0.11 344 0.016 364 0.12 345 0.012 365 0.020 346 0.025 366 0.024 347 0.022 367 0.011 348 0.013 368 0.024 349 0.021 369 0.022 350 0.020 370 0.017 351 0.019 371 0.015 352 0.013 372 0.033 353 0.023 373 0.013 354 0.013 374 0.013 355 0.015 375 0.012 356 0.016 376 0.014 357 0.019 377 0.012 358 0.017 378 0.018 359 0.015 379 0.021

[2082] 223 TABLE 223 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 380 0.023 409 0.020 381 0.011 410 0.018 382 0.015 411 0.015 383 0.013 412 0.019 384 0.016 413 0.026 385 0.019 414 0.024 386 0.018 415 0.019 387 0.025 416 0.024 388 0.020 417 0.029 389 0.012 418 0.016 390 0.014 419 0.021 391 0.017 420 0.015 392 0.014 421 0.017 393 0.011 422 0.017 394 0.019 423 0.017 395 0.016 424 0.020 396 0.025 425 0.026 397 0.037 426 0.053 398 0.077 427 0.020 399 0.032 428 0.026

[2083] 224 TABLE 224 HCV polymerase HCV polymerase Ex. inhibitory activity Ex. inhibitory activity No. IC50 [&mgr;M] No. IC50 [&mgr;M] 429 0.017 442 0.024 430 0.017 443 0.030 431 0.015 445 0.33 432 0.022 446 0.016 433 0.014 502 0.024 434 0.011 503 0.196 435 0.012 601 0.32 436 0.026 701 0.052 440 0.070

[2084] 225 TABLE 225 Example No. 341 1H NMR(&dgr;) ppm 1256 300MHz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.25(1H, d, J=8.7Hz), 8.03(1H, dd, J=8.7Hz), 7.72 and 7.22(4H, Abq, J=8.8Hz), 7.67(1H, d, # J=1.5Hz), 7.52(4H, s), 7.49(1H, dd, J=7.9, 1.5Hz), 7.43(1H, d, J=7.9Hz), 4.46(1H, brs), 4.35(1H, brt, J=12.4Hz), 3.62(1H, brs), 3.06(1H, brs), 2.79(1H, brs), 2.38-2.20(2H, brm), 2.08-1.81(4H, brm), 1.77-1.52(4H, brm), 1.46-1.20(3H, brm), 1.19-1.00(2H, brm), 0.94 and 0.92(total 3H, each s) Purity >90% (NMR) MS 662(M + 1) Example No. 342 1H NMR(&dgr;) ppm 1257 300Mz, DMSO-d6 8.28(1H, d, J=1.5Hz), 8.26(1H, d, J=1.8Hz), 8.19(1H, d, J=8.8Hz), 8.07(1H, dd, J=7.7, 1.8Hz), 8.00(1H, dd, J=8.8, 1.5Hz), 7.70 # and 7.22(4H, Abq, J=8.8Hz), 7.56-7.50(1H, m), 7.56(4H, s), 5.17(2H, s), 4.33(1H, brt, J=12.5Hz), 2.05(3H, s), 2.37-2.20(2H, brm), 2.06-1.80(4H, brm), 1.70-1.60(1H, brm), 1.50-1.20(3H, brm) Purity >90% (NMR) MS 679(M + 1) Example No. 343 1H NMR(&dgr;) ppm 1258 300MHz, DMSO-d6 8.20(1H, d, J=1.5Hz), 7.93(1H, d, J=8.6Hz), 7.84(1H, dd, J=8.3Hz, 1.5Hz), 7.57(2H, d, J=8.6Hz), 7.50-7.40(4H, m), 7.27(1H, # d, J=8.2Hz), 7.22(1H, d, J=2.6Hz), 7.10(2H, d, J=8.6Hz) 7.01(1H, dd, J=8.6Hz, 2.6Hz), 5.02(2H, s), 4.89(2H, s), 4.78(1H, d, J=4.1Hz), 4.38-4.18(1H, m), 3.96-3.81(1H, m), 3.78-3.62(2H, m), 3.27-2.99(2H, m), 2.35-1.15(14H, m) Purity >90% (NMR) MS 694(M + 1)

[2085] 226 TABLE 226 Example No. 344 1H NMR(&dgr;) ppm 1259 300MHz, DMSO-d6 8.30(1H, s), 8.23(1H, d, J=8.7Hz), 8.02(1H, d, J=8.4Hz), 7.71(2H, d, J=8.7Hz), 7.55-7.15(8H, m), 7.07(1H, dd, J=8.4Hz, 3.0Hz), 5.07(2H, s), 4.35(1H, m), 4.17(2H, t, J=4.5Hz), 3.69(2H, t, J=4.5Hz), 3.32(3H, s), 2.40-2.15(2H, m), 2.10-1.80(4H, m), 1.75-1.60(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 611(M + 1) Example No. 345 1H NMR(&dgr;) ppm 1260 300MHz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.22(1H, d, J=8.7Hz), 8.01(1H, d, J=8.7Hz), 7.70(1H, d, J=8.7Hz), 7.50-7.15(8H, m), 7.07(1H, dd, # J=8.4Hz, 2.4Hz), 5.07(2H, s), 4.35(1H, m), 4.17(2H, t, J=4.2Hz), 3.76(2H, t, J=4.5Hz), 3.65-3.40(4H, m), 3.25(3H, s), 2.40-2.20(2H, m), 2.10-1.80(4H, m), 1.75-1.65(1H, m), 1.65-1.20(3H, m) Purity >90% (NMR) MS 655(M + 1) Example No. 346 1H NMR(&dgr;) ppm 1261 300Mz, DMSO-d6 8.26(1H, d, J=1.9Hz), 8.23(1H, d, J=1.5Hz), 8.08-8.02(2H, m), 7.91(1H, dd, J=8.7, 1.5Hz), 7.63 and 7.16(4H, Abq, # J=8.9Hz), 7.56-7.51(5H, m), 5.15(2H, s), 4.29(1H, brt, J=11.7Hz), 2.96(2H, d, J=6.9Hz), 2.37-2.12(3H, m), 2.00-1.79(4H, brm), 1.71-1.60(1H, brm) 1.49-1.19(3H, brm), 0.97 and 0.95 (total 6H, each s) Purity >90% (NMR) MS 621(M + 1)

[2086] 227 TAB1E 227 Example No. 347 1H NMR(&dgr;) ppm 1262 300Mz, DMSO-d6 8.26(1H, s), 8.22(1H, s), 8.06(1H, s), 8.05(1H, d, J=8.0Hz), 7.94 and 7.85(2H, ABq, J=8.8Hz), 7.59 and 7.15(4H, A′ B′ q, J=8.6Hz), 7.52(4H, # s), 7.44(1H, d, J=8.0Hz), 5.12(2H, s), 4.27(1H, brt, J=11.4Hz), 2.38-2.18(2H, brm), 1.97-1.77(4H, brm), 1.70-1.59(1H, brm), 1.49-1.17(3H, brm) Purity >90% (NMR) MS 634(M + 1) Example No. 348 1H NMR(&dgr;) ppm 1263 300MHz, DMSO-d6 8.32(1H, s), 8.29(1H, d, J=9.0Hz), 8.06(1H, d, J=8.7Hz), 7.74(2H, d, J=9.0Hz), 7.72(1H, brs), 7.60-7.45(5H, m), 7.42(1H, d, J=7.8Hz), 7.24(2H, d, J=8.7Hz), 5.15(2H, s), 4.37(1H, m), 4.00-3.10(6H, m), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.20(6H, m) Purity >90% (NMR) MS 680(M + 1) Example No. 349 1H NMR(&dgr;) ppm 1264 300MHz, DMSO-d6 8.41(1H, d, J=1.5Hz), 8.33(1H, d, J=1.5Hz), 8.26(1H, d, J=8.7Hz), 8.18(1H, dd, J=2.0Hz, 8.0Hz), 8.04(1H, dd, J=1.5Hz, 9.0Hz), 7.75(2H, # d, J=8.7Hz), 7.63(1H, d, J=8.1Hz), 7.62-7.45(4H, m), 7.26(2H, d, J=8.7Hz), 5.25(2H, s), 4.35(1H, m), 2.45(3H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 619(M + 1)

[2087] 228 TABLE 228 Example No. 350 1H NMR(&dgr;) ppm 1265 300MHz, DMSO-d6 8.36(1H, d, J=7.7Hz), 8.29(1H, s), 8.23(1H, d, J=8.8Hz), 8.02(1H, d, J=8.6Hz), 7.94(1H, d, J=7.9Hz), 7.84(1H, d, J=1.6Hz), 7.80-7.65(3H, m), 7.53(4H, s), 5.15(2H, s), 4.34(1H, m), 4.12(1H, m), 2.35-2.20(2H, m), 2.10-1.60(5H, m), 1.50-1.20(3H, m), 1.17(6H, d, J=6.5Hz) Purity >90% (NMR) MS 622(M + 1) Example No. 351 1H NMR(&dgr;) ppm 1266 300MHz, DMSO-d6 8.29(1H, s), 8.24(1H, d, J=8.8Hz), 8.02(1H, d, J=8.6Hz), 7.80-7.65(3H, m), 7.55-7.45(5H, m), 7.32(1H, d, J=1.5Hz), 7.22(2H, d, J=8.8Hz), 5.13(2H, s), 4.35(1H, m), 3.60(2H, m), 3.33(2H, m), 2.40-2.15(2H, m), 2.10-1.15(14H, m) Purity >90% (NMR) MS 648(M + 1) Example No. 352 1H NMR(&dgr;) ppm 1267 300MHZ, DMSO-d6 13.20(1H, brs), 8.30-8.24(2H, m), 8.13(1H, s), 8.04(1H, d, J=8.7Hz), 7.94(1H, d, J=8.0Hz), 7.75-7.70(3H, m), 7.55-7.43(5H, m), 7.25(2H, d, J=8.7Hz), 5.13(2H, s), 4.36(1H, m), 3.53(2H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(9H, m) Purity >90% (NMR) MS 652(M + 1)

[2088] 229 TABLE 229 Example No. 353 1H NMR(&dgr;) ppm 1268 300MHz, DMSO-d6 8.41(1H, s), 8.33-8.29(2H, m), 8.16(1H, d, J=8.2Hz), 8.07(1H, d, J=8.6Hz), 7.77(2H, d, J=8.7Hz), 7.62(1H, d, J=8.0Hz), 7.59-7.51(4H, m), 7.28(2H, d, J=8.8Hz), 5.21(2H, s), 4.56(2H, s), 4.37(1H, m), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(9H, m) Purity 90% (NMR) MS 634(M + 1) Example No. 354 1H NMR(&dgr;) ppm 1269 300MHz, DMSO-d6 8.31(1H, s), 8.25(1H, d, J=9.0Hz), 8.03(1H, d, J=8.7Hz), 7.76-7.71(3H, m), 7.51-7.47(5H, m), 7.33(1H, s), 7.23(2H, d, J=9.0Hz), 5.14(2H, s), 4.36(1H, m), 4.02(1H, m), 3.75(1H, m), 3.56(1H, m), 3.22(2H, m), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.55(5H, m), 1.50-1.20(5H, m) Purity >90% (NMR) MS 664(M + 1) Example No. 355 1H NMR(&dgr;) ppm 1270 300MHz, DMSO-d6 8.62(1H, t, J=5.7Hz), 8.32-8.30(2H, m), 8.25(1H, d, J=8.7Hz), 8.03(1H, d, J=8.7Hz), 7.96(1H, d, J=8.1Hz), 7.86(1H, s), 7.75(1H, d, # J=9.0Hz), 7.72(2H, d, J=9.0Hz), 7.55-7.50(4H, m), 7.22(2H, d, J=9.0Hz), 5.17(2H, s), 4.35(1H, m), 3.52(2H, t, J=6.0Hz), 3.36(2H, t, J=6.0Hz), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 624(M + 1)

[2089] 230 TABLE 230 Example No. 356 1H NMR(&dgr;) ppm 1271 300Mz, DMSO-d6 9.30(1H, t, J=5.9Hz), 8.54(2H, d, J=5.9Hz), 8.22(1H, s), 8.02-7.79(5H, m), 7.59 and 7.12(4H, ABq, J=8.6Hz), 7.55(4H, s), 7.37(2H, d, J=5.9Hz), 5.15(2H, s), 4.54(2H, d, J=5.7Hz), 4.26(1H, brt, J=12.8Hz), 2.36-2.18(2H, brm), 1.97-1.78(4H, brm), 1.70-1.60(1H, brm), 1.47-1.17(3H, brm) Purity >90% (NMR) MS 671(M + 1) Example No. 357 1H NMR(&dgr;) ppm 1272 300Mz, DMSO-d6 8.31(1H, d, J=1.5Hz), 8.43(1H, d, J=8.4Hz), 8.03(1H, dd, J=8.4, 1 5Hz), 7.74(1H, d, J=8.1Hz), 7.73 and 7.23(4H, ABq, J=9.0Hz), 7.54-7.51(5H, m), 7.37(1H, d, J=1.8Hz), 5.14(2H, s), 4.36(1H, brt, J=12.1Hz), 2.98(6H, brs), 2.37-2.20(2H, brm), 2.08-1.81(4H, brm), 1.70-1.60(1H, brm), 1.50-1.21(3H, brm) Purity >90% (NMR) MS 608(M + 1) Example No. 358 1H NMR(&dgr;) ppm 1273 300MHz, DMSO-d6 8.33(1H, s), 8.31(1H, d, J=8.7Hz), 8.14(1H, s), 8.07(1H, d, J=8.7Hz), 7.92(1H, d, J=8.0Hz), 7.76(2H, d, J=8.7Hz), 7.52-7.40(5H, m), 7.31-7.26(3H, m), 5.15(2H, s), 4.37(1H, m), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m) Purity 90% (NMR) MS 635(M + 1)

[2090] 231 TABLE 231 Example No. 359 1H NMR(&dgr;) ppm 1274 300MHz, DMSO-d6 8.31(1H, s), 8.25(1H, d, J=8.7Hz), 8.10-7.90(2H, m), 7.82(1H, dd, J=7.8Hz, 1.8Hz), 7.72(2H, d, J=9.0Hz), 7.63(1H, d, J=8.1Hz), 7.23(2H, d, J=9.0Hz), 5.25(2H, s), 4.34(1H, m), 3.65-3.50(1H, m), 3.20-3.05(2H, m), 2.90-2.75(2H, m), 2.40-2.15(2H, m), 2.10-1.10(12H, m) Purity >90% (NMR) MS 700(M + 1) Example No. 360 1H NMR(&dgr;) ppm 1275 300MHz, DMSO-d6 8.33(1H, s), 8.30(1H, d, J=8.5Hz), 8.06(1H, d, J=10.1Hz), 8.80-8.65(3H, m), 8.60-8.45(3H, m), 7.42(1H, d, J=7.8Hz), 7.35-7.15(4H, m), 5.15(2H, s), 4.36(1H, m), 3.01, 2.97(6H, s), 2.40-2.15(2H, m), 2.10-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 592(M + 1) Example No. 361 1H NMR(&dgr;) ppm 1276 300MHz, DMSO-d6 8.35-8.20(2H, m), 8.05(1H, d, J=8.7Hz), 8.80-8.65(3H, m), 7.60-7.40(3H, m), 7.40-7.30(5H, m), 5.17(2H, s), 4.35(1H, m), 3.01, 2.97(6H, s), 2.40-2.15(2H, m), 2.10-1.80(4H, m), 1.70-1.20(4H, m) Purity >90% (NMR) MS 592(M + 1)

[2091] 232 TABLE 232 Example No. 362 1H NMR(&dgr;) ppm 1277 300MHz, DMSO-d6 8.33(1H, s), 8.29(1H, d, J=8.7Hz), 8.06(1H, d, J=8.7Hz), 7.79(2H, d, J=9.0Hz), 7.76(1H, d, J=9.0Hz), 7.60(1H, d, J=8.1Hz), 7.53(1H, dd, J=1.7Hz, 8.0Hz), 7.35(2H, d, J=8.7Hz), 6.85-6.80(2H, m), 5.29(2H, s), 4.38(1H, m), 3.01, 2.96(6H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 614(M + 1) Example No. 363 1H NMR(&dgr;) ppm 1278 300MHz, DMSO-d6 8.28(1H, d, J=1.3Hz), 8.20-8.10(2H, m), 8.98(1H, d, J=8.6Hz), 7.90-7.80(2H, m), 7.75(2H, d, J=8.7Hz), 7.36(2H, d, J=8.7Hz), 7.04(1H, d, J=1.3Hz), 5.35(2H, s), 4.36(1H, m), 2.39(3H, s), 2.35-2.15(2H, m), 2.05-1.75(4H, m), 1.70-1.60(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 586(M + 1) Example No. 364 1H NMR(&dgr;) ppm 1279 300MHz, DMSO-d6 8.31(1H, s), 8.26(1H, d, J=8.7Hz), 8.13(1H, s), 8.04(1H, d, J=9.0Hz), 7.90-7.70(4H, m), 7.65(1H, s), 7.39(2H, d, J=9.0Hz), 5.37(2H, s), 4.38(1H, m), 2.40-2.20(2H, m), 2.15-2.00(2H, m), 1.95-1.80(2H, m), 1.75-1.60(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 604(M + 1)

[2092] 233 TABLE 233 Example No. 365 1H NMR(&dgr;) ppm 1280 300MHz, DMSO-d6 8.28(1H, s), 8.23(1H, s), 8.17(1H, d, J=8.7Hz), 8.00(2H, t, J=6.9Hz), 7.69(2H, d, J=8.4Hz), 7.60-7.45(5H, m), 7.21(2H, d, J=8.4Hz), 7.05(1H, s) 5.19(2H, s), 4.33(1H, m), 2.41(3H, s), 2.40-2.20(2H, m), 2.10-1.80(4H, m), 1.70-1.60(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 618(M + 1) Example No. 366 1H NMR(&dgr;) ppm 1281 300MHz, DMSO-d6 8.26(1H, s), 8.17(1H, s), 8.11(1H, d, J=8.7Hz), 7.95(2H, d, J=9.6Hz), 7.70-7.40(8H, m), 7.19(2H, d, J=8.4Hz), 5.18(2H, s), 4.30(1H, m), 2.51(3H, s), 2.40-2.15(2H, m), 2.05-1.80(4H, m), 1.75-1.60(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 634(M + 1) Example No. 367 1H NMR(&dgr;) ppm 1282 300Mz, DMSO-d6 8.42(1H, d, J=1.9Hz), 8.30(1H, J=, 1.5Hz), 8.27(1H, d, J=8.7Hz), 8.18(1H, dd, # J=7.9, 1.9Hz), 8.04(1H, dd, J=8.7, 1.5Hz), 7.75 and 7.29(4H, ABq, J=8.9Hz) 7.63(1H, d, J=7.9Hz), 5.23(2H, s), 4.36(1H, brt, J=12.3Hz) 2.37-2.20(2H, brm), 2.08-1.80(4H, brm), 1.71-1.60(1H, brm), 1.51-1.21(3H, brm) Purity >90% (NMR) MS 605(M + 1)

[2093] 234 TABLE 234 Example No. 368 1H NMR(&dgr;) ppm 1283 300Mz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.25(1H, d, J=8.6Hz), 8.04(1H, dd, J=8.6, 1.5Hz), 7.93 and 7.67(4H, ABq, J=8.1Hz), 7.80(1H, # d, J=2.2Hz), 7.72 and 7.21(4H, A′ B′ q, J=8.6Hz), 7.60(1H, dd, J=8.1, 2.2Hz), 7.44(1H, d, J=8.1Hz), 5.13(2H, s), 4.34(1H, brt, J=11.7Hz), 2.37-2.19(2H, brm), 2.09-1.80(4H, brm), 1.72-1.60(1H, brm), 1.50-1.21(3H, brm) Purity >90% (NMR) MS 562(M + 1) Example No. 369 1H NMR(&dgr;) ppm 1284 300Mz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.25(1H, d, J=8.6Hz), 8.16 and 7.72(4H, ABq, J=8.4Hz), 8.13(1H, dd, J=8.6, 1.5Hz), 7.80(1Hd, J=2.2Hz), 7.70 and 7.24(4H, A′ B′ q, J=8.8Hz), # 7.61(1H, dd, J=8.1, 2.2Hz), 7.48(1H, d, J=8.1Hz), 5.17(2H, s), 4.33(1H, brt, J=12.1Hz), 2.36-2.18(2H, brm), 2.08-1.77(4H, brm), 1.69-1.57(1H, brm), 1.49-1.17(3H, brm) Purity >90% (NMR) MS 605(M + 1) Example No. 370 1H NMR(&dgr;) ppm 1285 300MHz, DMSO-d6 10.94(1H, brs), 8.33(1H, s), 8.27(1H, d, J=8.7Hz), 8.04(1H, d, J=8.7Hz), 7.74(2H, d, J=8.4Hz), 7.56-7.29(6H, m), 7.23(2H, d, J=8.7Hz), 7.13(1H, d, J=8.7Hz), 5.08(2H, s), 4.51(2H, brs), 4.36(1H, m), 3.94(1H, brs), 3.75-3.00(6H, m), 3.20-1.20(14H, m) Purity >90% (NMR) MS 680(M + 1)

[2094] 235 TABLE 235 Example No. 371 1H NMR(&dgr;) ppm 1286 300MHz, DMSO-d6 8.31(1H, d, J=1.5Hz), 8.17(1H, d, J=9.0Hz), 7.99(1H, dd, J=8.7Hz, 1.4Hz), 7.70-7.55(2H, m), 7.50-7.30(6H, m), 7.19(1H, dd, J=12.0Hz, # 2.2Hz), 7.06(1H, dd, J=8.6Hz, 2.2Hz), 5.08(2H, 4.10(1H, m), 3.68(2H, brt, J=5.2), 2.50(2H, brt, J=1.8Hz), 2.30-2.10(2H, m), 2.00-1.75(8H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 652(M + 1) Example No. 372 1H NMR(&dgr;) ppm 1287 300Mz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.11(1H, d, J=8.6Hz), 7.96(1H, dd, J=8.6, 1.5Hz), 7.89(1H, s), 7.78 and 7.56(4H, ABq, J=8.4Hz), 7.69(1H, s), 7.66(1H, t, # J=8.8Hz), 7.31(1H, dd, J=12.1, 2.2Hz), 7.18(1H, dd, J=8.8, 2.2Hz), 5.37(2H, s), 4.08(1H, brt, J=11.0Hz), 3.02(3H, s), 2.96(3H, s), 2.31-2.14(2H, brm), 1.95-1.77(4H, brm,) 1.69-1.59(31H, brm), 1.46-1.18(3H, brm) Purity >90% (NMR) MS 626(M + 1) Example No. 373 1H NMR(&dgr;) ppm 1288 300MHz, DMSO-d6 11.40(1H, brs), 9.25(2H, brs), 8.29(1H, d, J=1.3Hz), 8.12-8.09(2H, m), 7.96(1H, d, J=8.7Hz), 7.88(1H, dd, J=1.8Hz, 8.1Hz), 7.67-7.63(2H, m), 7.56(2H, # d, J=8.7Hz), 7.51(2H, d, J=8.7Hz), 7.17(1H, d, J=12.0Hz), 7.05(1H, d, J=8.6Hz), 5.16(2H, s), 4.05(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 613(M + 1)

[2095] 236 TABLE 236 Example No. 374 1H NMR(&dgr;) ppm 1289 300MHz, DMSO-d6 13.21(1H, brs), 8.31(1H, d, J=1.4Hz), 8.18-8.15(2H, m), 7.99(1H, d, J=8.7Hz), 7.94(1H, dd, J=1.8Hz, 8.0Hz), 7.70-7.53(6H, m), 7.17(1H, d, J=12.0Hz), 7.05(1H, d, J=8.6Hz), 5.20(2H, s), 4.09(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 639(M + 1) Example No. 375 1H NMR(&dgr;) ppm 1290 300MHz, DMSO-d6 8.32(1H, d, J=1.5Hz), 8.23(1H, z), J=1.5Hz), 8.19(1H, d, J=9.0Hz), 8.03-7.98(2H, m), 7.68(1H, t, J=8.4Hz), 7.60(1H, d, J=8.1Hz), 7.56(2H, d, J=9.3Hz), 7.53(2H, d, J=9.0Hz), 7.22(1H, dd, J=2.1Hz, 12.0Hz), 7.09(1H, dd, J=2.1Hz, 8.4Hz), 5.21(2H, s), 4.12(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 658(M + 1) Example No. 376 1H NMR(&dgr;) ppm 1291 300MHz, DMSO-d6 13.61(1H, brs), 8.34-8.30(2H, m), 8.21(1H, d, J=8.7Hz), 8.07(1H, dd, J=1.8Hz, 8.1Hz), 8.02(1H, dd, J=1.5Hz, 8.7Hz), 7.69(1H, t, J=8.4Hz), 7,57-7.49(5H, m), 7.22(1H, dd, J=2.7Hz, 12.0Hz), 7.09(1H, dd, J=2.4Hz, 9.0Hz), 5.19(2H, s), 4.12(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 655(M + 1)

[2096] 237 TABLE 237 Example No. 377 1H NMR(&dgr;) ppm 1292 300Mz, DMSO-d6 8.60(1H, d, J=4.5Hz), 8.29(1H, d, J=1.5Hz), 8.14(1H, d, J=8.9Hz), 8.13(1H, d, # J=1.5Hz), 7.98(1H, dd, J=8.9, 1.5Hz), 7.94(1H, dd, J=8.1, 1.5Hz), 7.64(1H, t, J=8.7Hz), 7.52 and 7.49(4H, ABq, J=9.0Hz), 7.46(1H, d, J=8.1Hz), 7.18(1H, dd, J=12.1, 2.3Hz), 7.05(1H, dd, J=8.7, 2.3Hz), 5.13(2H, s), 4.08(1H, brt, J=12.1H), 2.95-2.84(1H, ,), 2.31-2.14(2H, brm), 1.97-1.78(4H, brm), 1.72-1.59(1H, brm), 1.47-1.21(3H, brm), 0.76-0.58(4H, m) Purity >90% (NMR) MS 638(M + 1) Example No. 378 1H NMR(&dgr;) ppm 1293 300Mz, DMSO-d6 8.77(1H, d, J=1.4Hz), 8.30(1H, d, J=1.4Hz), 8.16(1H, d, # J=1.8Hz), 8.13(1H, d, J=8.4Hz), 7.98(2H, dd, J=8.4, 1.8Hz), 7.65(1H, t, J=8.4Hz), 7.53 and 7.49(4H, ABq, J=8.8Hz), 7.47(1H, d, J=7.7Hz), 7.18(1H, dd, J=12.1, 2.2Hz), 7.05(1H, dd, J=8.4, 2.2Hz), 5.13(2H, s), 4.53-4.40(1H, m), 4.09(1H, brt, J=12.8Hz), 2.31-2.02(6H, brm), 1.96-1.80(4H, brm), 1.78-1.60(3H, brm), 1.47-1.21(3H, brm) Purity >90% (NMR) MS 652(M + 1) Example No. 379 1H NMR(&dgr;) ppm 1294 300Mz, DMSO-d6 8.29(1H, d, J=1.1Hz), 8.11(1H, d, J=1.5Hz), 8.11(1H, d, J=8.8Hz), 7.98-7.91(2H, m), 7.89(1H, s), 7.63(1H, t, J=8.8Hz), 7.52 and 7.48(4H, ABq, J=8.6Hz), 7.44(1H, d, J=8.1Hz), 7.17(1H, dd, J=12.1, 2.2Hz), 7.04(1H, dd, J=8.8, 2.2Hz), 5.12(2H, s), 4.07(1H, brt, J=12.4Hz), 2.33-2.14(2H, brm), 1.96-1.79(4H, brm), 1.70-1.60(1H, # brm), 1.48-1.21(3H, brm), 1.41(9H, s) Purity >90% (NMR) MS 654(M + 1)

[2097] 238 TABLE 238 Example No. 380 1H NMR(&dgr;) ppm 1295 300Mz, DMSO-d6 8.62(1H, t, J=5.5Hz), 8.30(1H, d, J=1.5Hz), 8.17(1H, d, J=1.8Hz), 8.14(1H, d, J=8.8Hz), 7.98(1H, # dd, J=8.1, 1.8Hz), 7.64(1H, t, J=8.8Hz), 7.52 and 7.50(4H, ABq, J=8.8Hz), 7.48(1H, d, J=8.1Hz), 7.18(1H, dd, J=12.1, 2.2Hz), 7.05(1H, dd, J=8.8, 2.2Hz), 5.14(2H, s), 4.08(1H, brt, J=12.1Hz), 3.13(1H, t, J=6.2Hz), 2.31-2.14(2H, brm), 1.97-1.78(5H, brm), 1.70-1.60(1H, brm), 1.47-1.21(3H, brm), 0.92(3H, s), 0.90(3H, s) Purity >90% (NMR) MS 654(M + 1) Example No. 381 1H NMR(&dgr;) ppm 1296 300Mz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.27(1H, d, J=8.3Hz), 8.18(1H, d, # J=1.9Hz), 8.13(1H, d, J=8.7Hz), 8.01-7.96(2H, m), 7.64(1H, t, J=8.7Hz), 7.52 and 7.49(1H, ABq, J=8.8Hz), 7.49(1H, d, J=7.9Hz), 7.18(1H, dd, J=12.1, 2.3Hz), 7.05(1H, dd, J=8.7, 2.3Hz), 5.13(2H, s), 4.12-4.00(2H, m), 3.52-3.34(2H, m), 2.31-2.14(2H, brm), 1.97-1.79(4H, brm), 1.71-1.60(1H, brm), 1.48-1.21(3H, m, 1.17 and 1.15(total 3H, each s) Purity >90% (NMR) MS 656(M + 1) Example No. 382 1H NMR(&dgr;) ppm 1297 300Mz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.13(1H, d, J=8.8Hz), 8.09(1H, d, J=1.5Hz), 7.98(1H, dd, J=8.8, 1.5Hz), 7.86(1H, dd, J=8.1, 1.5Hz), 7.64(1H, J=8.8Hz), 7.55-7.47(5H, m), 7.17(1H, dd, J=12.1, 2.2Hz), 7.05(1H, dd, J=8.8, 2.2Hz), 5.14(2H, s), 4.08(1H, brt, J=12.8 Hz), 3.75(3H, s), 2.32-2.14(2H, brm), 1.96-1.78(4H, # brm), 1.70-1.59(1H, brm), 1.47-1.21(3H, brm) Purity >90% (NMR) MS 628(M + 1)

[2098] 239 TABLE 239 Example No. 383 1H NMR(&dgr;) ppm 1298 300Mz, DMSO-d6 8.57(1H, t, J=5.5Hz), 8.29(1H, d, J=1.4Hz), 8.19(1H, d, J=1.5Hz), 8.12(1H, # d, J=9.2Hz), 8.01-7.95(2H, m), 7.64(1H, t, J=8.8Hz), 7.53 and 7.50(4H, ABq, J=8.8Hz), 7.48(1H, d, J=7.7Hz), 7.17(1H, dd, J=12.1, 2.2Hz), 7.04(1H, dd, J=8.8, 2.2Hz), 5.14(2H, s), 4.08(1H, brt, J=13.9Hz), 3.70-3.66(1H, m), 3.48-3.36(3H, m), 3.28-3.20(1H, m), 2.32-2.13(2H, brm), 1.96-1.79(4H, brm), 1.71-1.60(1H, brm), 1.47-1.19(3H, brm) Purity >90% (NMR) MS 672(M + 1) Example No. 384 1H NMR(&dgr;) ppm 1299 300Mz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.14(1H, d, J=8.4Hz), 7.98(1H, dd, J=8.4, 1.5Hz), 7.68(1H, brs), 7.63(1H, # t, J=8.4Hz), 7.51(5H, s), 7.43(1H, d, J=8.1Hz), 7.17(1H, dd, J=12.5, 1.8Hz), 7.03(1H, dd, J=8.4, 1.8Hz), 4.08(1H, brt, J=11.4Hz), 3.50 and 3.30(total 2H, each brs), 2.97(3H, brs), 2.33-2.13(2H, brm), 1.96-1.79(4H, brm), 1.70-1.59(1H, brm), 1.47-1.03(6H, brm), Purity >90% (NMR) MS 640(M + 1) Example No. 385 1H NMR(&dgr;) ppm 1300 300Mz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.12(1H, d, J=8.8Hz), 7.97(1H, dd, J=8.8, 1.5Hz), 7.72-7.60(2H, m), 7.55-7.42(6H, m), 7.16(1H, d, J=11.7Hz), 7.03(1H, d, J=8.4Hz), 5.15(2H, s), 4.07(1H, brt, J=12.5Hz), 3.44 and 3.22(total 2H, each s), 2.97(3H, brs), 2.32-2.13(2H, brm), 1.72-1.50(3H, brm), 1.47-1.23(3H, brm), 0.93 and 0.72(total 3H, each brs) Purity >90% (NMR) MS 654(M + 1)

[2099] 240 TABLE 240 Example No. 386 1H NMR(&dgr;) ppm 1301 300Mz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.12(1H, d, J=8.7Hz), 7.97(1H, dd, J=8.7, 1.5Hz)7.74-7.60(2H, m), 7.54-7.42(6H, m), 7.17(1H, dd, J=12.1, 2.2Hz), 7.02(1H, dd, J=8.3, 2.2Hz), 5.15(2H, s), 4.06(1H, brt, J=12.8Hz), 3.92(1H, brs), 2.85(3H, brs), 2.32-2.14(2H, brm), 1.96-1.79(4H, brm), 1.70-1.59(1H, brm), 1.46-1.07(3H, brm), 1.15(6H, brs) Purity >90% (NMR) MS 654(M + 1) Example No. 387 1H NMR(&dgr;) ppm 1302 300Mz, DMSO-d6 8.29(1H, s), 8.14 and 7.97(2H, ABq, J=8.7Hz), 7.63(1H, s), 7.63(1H, t, J=8.7Hz), 7.51-7.41(6H, m), 7.16(1H, dd, J=12.1, 1.9Hz), 7.02(1H, dd, J=8.7, 1.9Hz), 5.16(2H, s), 4.26(2H, brs), 4.07(1H, brt, J=12.1Hz), 2.32-2.14(2H, brm), 1.97-1.78(5H, brm) 1.70-1.15(9H, brm), 1.24(3H, s), 1.21(3H, s) Purity >90% (NMR) MS 694(M + 1) Example No. 388 1H NMR(&dgr;) ppm 1303 300MHz, DMSO-d6 628.58(1H, m), 8.29(1H, s), 8.20-8.10(2H, m), 8.05-7.90(2H, m), 7.64(1H < t, J=8.4Hz), 7.60-7.40(5H, m), 7.15(1H, d, J=12.3Hz), 7.04(1H, d, J=8.4Hz), 5.13(2H, s), 4.08(1H, m), 3.40-3.20(2H, m), 2.35-2.10(2H, m), 2.00-1.20(12H, m), 0.91(3H, t, J=6.9Hz) Purity >90% (NMR) MS 654(M + 1)

[2100] 241 TABLE 241 Example No. 389 1H NMR(&dgr;) ppm 1304 300MHz, DMSO-d6 8.60(1H, m), 8.29(1H, s), 8.20-7.90(4H, m), 7.64(1H, t, J=9.0Hz), 7.60-7.40(5H, m), 7.17(1H, d, J=12.0Hz), 7.04(1H, d, J=8.7Hz), 5.13(2H, s), 4.80(1H, m), 3.35-3.15(2H, m), 2.30-2.05(2H, m), 2.00-1.10(10H, m), 0.91(3H, t, J=7.5Hz) Purity >90% (NMR) MS 640(M + 1) Example No. 390 1H NMR(&dgr;) ppm 1305 300MHz, DMSO-d6 8.62(1H, m), 8.30(1H, s), 8.20-8.10(2H, m), 8.05-7.90(2H, m), 7.65(1H, t, J=8.4Hz), 7.60-7.40(5H, m), 7.18(1H, d, J=12.0Hz), 7.05(1H, d, J=8.4Hz), 5.14(2H, s), 4.09(1H, m), 3.40-3.20(2H, m), 2.35-2.10(2H, m), 2.00-1.80(4H, m), 1.75-1.60(1H, m), 1.45-1.20(3H, m), 1.15(3H, t, J=7.2Hz) Purity >90% (NMR) MS 626(M + 1) Example No. 391 1H NMR(&dgr;) ppm 1306 400NHz, DMSO-d6 8.54(1H, s), 8.31(1H, s), 8.19(1H, d, J=8.6Hz), 8.01(1H, d, J=8.6Hz), 7.81(1H, d, J=2.1Hz), 7.64(1H, # t, J=8.4Hz), 7.61(1H, dd, J=2.3Hz, 8.4Hz), 7.47(2H, d, J=8.6Hz), 7.43(2H, d, J=8.8Hz), 7.25(1H, d, J=8.4Hz), 7.17(1H, dd, J=2.3Hz, 12.1Hz), 7.05(1H, dd, J=2.3Hz, 8.6Hz), 5.05(2H, s), 4.12(1H, m), 2.96(6H, s), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 641(M + 1)

[2101] 242 TABLE 242 Example No. 392 1H NMR(&dgr;) ppm 1307 300Mz, DMSO-d6 8.79(1H, s), 8.29(1H, d, J=1.5Hz), 8.13(1H, d, J=8.8Hz), 7.98(1H, dd, J=8.8, # 1.5Hz), 7.80(1H, d, J=2.2Hz), 7.63(1H, t, J=8.4Hz), 7.61(1H, dd, J=8.2, 2.2Hz), 7.47 and 7.43(4H, ABq, J=8.8Hz), 7.26(1H, d, J=8.2Hz), 7.14(1H, dd, J=12.1, 2.2Hz), 7.02(1H, dd, J=8.4, 2.2Hz), 5.05(2H, s), 4.08(1H, brt, J=12.1Hz), 3.64-3.61(2H, m), 3.48-3.45(2H, m), 2.32-2.13(2H, brm), 1.96-1.78(4H, brm), 1.70-1.66(1H, brm), 1.44-1.19(3H, brm) Purity >90% (NMR) MS 683(M + 1) Example No. 393 1H NMR(&dgr;) ppm 1308 400MHz, DMSO-d6 8.94(1H, s), 8.31(1H, d, J=1.0Hz), 8.18(1H, d, J=8.6Hz), 8.00(1H, dd, J=1.4Hz, 8.8Hz), 7.71(1H, # d, J=2.2Hz), 7.66(1H, t, J=8.6Hz), 7.52(1H, dd, J=2.4Hz, 8.6Hz), 7.46(2H, d, J=8.6Hz), 7.42(2H, d, J=8.2Hz), 7.24(1H, d, J=8.4Hz), 7.16(1H, d, J=12.1Hz), 7.04(1H, dd, J=2.4Hz, 8.8Hz), 5.05(2H, s), 4.13(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 613(M + 1) Example No. 394 1H NMR(&dgr;) ppm 1309 300MHZ, DMSO-d6 8.93(1H, s), 8.31(1H, d, J=1.4Hz), 8.19(1H, d, J=8.8Hz), 8.01(1H, d, J=8.7Hz), 7.71(1H, d, # J=2.2Hz), 7.66(1H, t, J=8.5Hz), 7.51(1H, dd, J=2.2Hz, 8.4Hz), 7.46(2H, d, J=8.6Hz), 7.41(2H, d, J=8.7Hz), 7.23(1H, d, J=8.4Hz), 7.16(1H, d, J=12.2Hz), 7.05(1H, d, J=8.7Hz), 5.05(2H, s), 4.13(1H, m), 3.12(2H, q, J=7.2Hz), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.60(1H, m), 1.55-1.20(3H, m), 1.06(3H, t, J=7.2Hz) Purity >90% (NMR) MS 641(M + 1)

[2102] 243 TABLE 243 Example No. 395 1H NMR(&dgr;) ppm 1310 300MHz, DMSO-d6 8.83(1H, s), 8.32(1H, d, J=1.4Hz), 8.21(1H, d, J=8.8Hz), 8.02(1H, dd, J=1.4Hz, 8.7Hz), 7.71(1H, d, J=2.1Hz), 7.68(1H, t, # J=8.6Hz), 7.49(1H, dd, J=2.2Hz, 8.4Hz), 7.46(2H, d, J=8.4Hz), 7.41(2H, d, J=8.6Hz), 7.23(1H, d, J=8.4Hz), 7.17(1H, d, J=12.2Hz), 7.06(1H, d, J=8.7Hz), 6.30(1H, brs), 5.05(2H, s), 4.14(1H, m), 3.77(1H, sept, J=6.5Hz), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m), 1.11(6H, d, J=6.5Hz) Purity >90% (NMR) MS 655(M + 1) Example No. 396 1H NMR(&dgr;) ppm 1311 300MHz, DMSO-d6 8.37(1H, d, J=7.3Hz), 8.25(1H, s), 8.15(1H, s), 7.97(2H, d, J=8.8Hz), 7.88(1H, d, J=8.8Hz), 7.58-7.47(4H, m), 7.31(1H, m), 7.11(1H, dd, J=8.4, 2.2Hz), 6.98(1H, dd, J=8.4, 2.2), 5.13(2H, s), 4.13(1H, q, J=6.6Hz), 3.98(1H, m), 2.19(2H, m), 1.86(4H, m) 1.62(1H, m) 1.31(3H, m), 1.20(6H, d, J=6.6Hz) Purity >90% (NMR) MS 642(M + 1) Example No. 397 1H NMR(&dgr;) ppm 1312 300MHz, DMSO-d6 8.40(1H, d, J=7.9Hz), 8.28(1H, d, J=1.9Hz), 8.15(1H, d, J=1.9Hz), 8.11(1H, d, J=8.7Hz), 7.96(2H, m), 7.56(1H, t, J=8.7Hz), 7.45(3H, m), 7.18(1H, m), 7.08(1H, dd, J=12.1, 1.9Hz), 6.96(1H, dd, J=8.3, 2.3Hz), 5.09(2H, s), 4.14(1H, m), 4.04(1H, m), 2.23(2H, m), 1.86(3H, m), 1.62(1H, m), 1.33(3H, m), 1.20(6H, d, J=6.4Hz) Purity >90% (NMR) MS 642(M + 1)

[2103] 244 TABLE 244 Example No. 398 1H NMR(&dgr;) ppm 1313 8.41(1H, d, J=8.1Hz), 8.29(1H, d, J=1.5Hz), 8.17(1H, d, J=1.8Hz), 8.12(1H, d, J=8.4Hz), 8.01-7.95(2H, m), 7.67-7.62(2H, m), 7.55-7.51(3H, m), 7.19(1H, dd, J=12.1, 2.2Hz), 7.05(1H, dd, J=8.8, 2.2Hz), 5.13(2H, s), 4.10-4.00(2H, m), 2.32-2.13(4H, m), 1.71-1.60(1H, m), 1.49-1.14(3H, m), 1.21(3H, s), 1.19(3H, s) Purity >90% (NMR) MS 674(M + 1) Example No. 399 1H NMR(&dgr;) ppm 1314 300Mz, DMSO-d6 8.39(1H, d, J=7.7Hz), 8.29(1H, d, J=1.5Hz), 8.16(1H, d, J=1.8Hz), 8.11(1H, d, J=8.8Hz), 8.00-7.95(2H, m), 7.69-7.61(2H, m), 7.54-7.46(3H, m), 7.18(1H, dd, J=12.1, 2.2Hz), 7.04(1H, dd, J=8.8, 2.2Hz), 5.13(2H, s), 4.20-4.02(2H, m), 2.33-2.13(2H, brm), 1.97-1.80(4H, m), 1.72-1.61(1H, m), 1.44-1.13(3H, m), 1.21(3H, s), 1.19(3H, s) Purity >90% (NMR) MS 658(M + 1) Example No. 400 1H NMR(&dgr;) ppm 1315 300MHz, DMSO-d6 8.39(1H, d, J=7.7Hz), 8.29(1H, s), 8.17(1H, d, J=1.5Hz), 8.11(1H, d, J=8.8Hz), 7.98(2H, m), 7.73(2H, m), 7.64(1H, t, J=8.4Hz), 7.52(1H, d, J=8.0Hz), 7.46(1H, dd, J=8.4, 1.8Hz), 7.18(1H, dd, J=11.9, 2.0Hz), 7.05(1H, dd, J=8.6, 2.4Hz), 5.14(2H, s), 4.13(2H, m), 2.22(2H, m), 1.88(4H, m) 1.64(1H, m), 1.34(3H, m), 1.20(6H, d, J=6.6Hz) Purity >90% (NMR) MS 642(M + 1)

[2104] 245 TABLE 245 Example No. 401 1H NMR(&dgr;) ppm 1316 300MHz, DMSO-d6 8.38(1H, d, J=7.8Hz), 8.28(1H, s), 8.20-8.05(2H, m), 8.00-7.90(2H, m), 7.65-7.30(5H, m), 7.09(1H, d, J=12.3Hz), 6.97(1H, d, J=10.2Hz), 5.09(2H, s), 4.20-4.00(2H, m), 2.30-2.10(2H, m), 2.00-1.80(4H, m), 1.70-1.60(1H, m), 1.40-1.10(3H, m), 1.19(6H, d, J=6.6Hz) Purity >90% (NMR) MS 658(M + 1) Example No. 402 1H NMR(&dgr;) ppm 1317 300MHz, DMSO-d6 8.25(1H, s), 8.03(1H, d, J=8.7Hz), 7.91(1H, d, J=8.7Hz), 7.83(1H, s), 7.70-7.35(6H, m), 7.04(1H, d, J=12.0Hz), 6.93(1H, d, J=8.4Hz), 5.09(2H, s), 4.00(1H, m), 3.60-3.40(4H, m), 2.30-2.10(2H, m), 1.45-1.15(3H, m) Purity >90% (NMR) MS 670(M + 1) Example No. 403 1H NMR(&dgr;) ppm 1318 400MHz, DMSO-d6 8.25(1H, s), 8.08(1H, d, J=8.4Hz), 7.92(1H, d, J=9.2Hz), 7.79(1H, s), 7.66-7.49(4H, m), 7.42(1H, d, J=7.6Hz), 7.31-7.28(1H, m), 7.14(1H, d, J=11.3Hz), 6.99(1H, d, J=8.8Hz), 5.13(2H, s), 4.02(1H, m), 3.54-3.33(4H, m), 2.29-2.08(2H, m), 1.93-1.73(8H, m), 1.67-1.52(1H, m), 1.48-1.11(3H, m) Purity >90% (NMR) MS 670(M + 1)

[2105] 246 TABLE 246 Example No. 404 1H NMR(&dgr;) ppm 1319 400MHz, DMSO-d6 8.41(1H, d, J=7.6Hz), 8.32(1H, d, J=1.5Hz), 8.20(1H, d, # J=8.6Hz), 8.17(1H, d, J=1.7Hz), 8.00(1H, dt, J=8.8Hz, 1.5Hz), 7.71-7.64(2H, m), 7.54(1H, dd, J=10.3Hz, 1.9Hz), 7.32(1H, dd, J=8.2Hz, 1.9Hz), 7.22(1H, dd, J=12.1Hz, 2.3Hz), 7.08(1H, dd, J=8.6Hz), 2.3Hz), 5.17(2H, s), 4.15(1H, m), 2.31-2.14(2H, m), 1.99-1.70(4H, m), 1.70-1.60(1H, m), 1.46-1.20(3H, m), 1.19(6H, d, J=6.6Hz) Purity >90% (NMR) MS 658(M + 1) Example No. 405 1H NMR(&dgr;) ppm 1320 300MHz, DMSO-d6 8.32(1H, s), 8.19(1H, d, J=9.0Hz), 8.03-7.98(2H, m), 7.75(1H, dd, J=2.1Hz, 8.4Hz), 7.67(1H, t, J=8.6Hz), 7.40-7.36(3H, # m), 7.32(2H, d, J=8.4Hz), 7.19(1H, dd, J=2.1Hz, 12.3Hz), 7.07(1H, dd, J=2.1Hz, 8.7Hz), 5.11(2H, s), 4.12(1H, m), 4.12(1H, m), 3.90(2H, t, J=6.9Hz), 2.54(2H, t, J=8.1Hz), 2.50(3H, s), 2.40-2.05(4H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 650(M + 1) Example No. 406 1H NMR(&dgr;) ppm 1321 300MHz, DMSO-d6 8.34(1H, d, J=7.7Hz), 8.29(1H, s), 8.15(1H, s), 8.11(1H, d, J=8.8Hz), 7.97(2H, d, J=9.2Hz), 7.63(1H, t, J=8.8Hz), 7.47-7.31(5H, m), 7.18(1H, dd, J=12.4, 2.2Hz), 7.06(1H, dd, J=12.4, 2.2Hz), 5.13(2H, s), 4.13(2H, m), 1.96(2H, m), 1.87(4H, m), 1.62(1H, m), 1.34(3H, m), 1.20(6H, d, J=6.2Hz) Purity >90% (NMR) MS 652(M + 1)

[2106] 247 TABLE 247 Example No. 407 1H NMR(&dgr;) ppm 1322 400MHz, DMSO-d6 8.32(1H, d, J=1.4Hz), 8.20(1H, d, J=8.8Hz), 8.01(1H, dd, # J=1.6Hz, 8.8Hz), 7.90(1H, s), 7.67(1H, t,J=8.4Hz), 7.61(1H, s), 7.55-7.50(4H, m), 7.21(1H, dd, J=2.3Hz, 12.0Hz), 7.06(1H, dd, J=2.2Hz, 8.7Hz), 5.10(2H, s), 4.11(1H, m), 3.78(2H, t, J=6.7Hz), 3.47(2H, t, J=7.4Hz), 2.54-2.48(2H, m), 2.40-2.10(2H, m), 2.00-1.80(4H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 708(M + 1) Example No. 408 1H NMR(&dgr;) ppm 1323 400MHz, DMSO-d6 8.32(1H, d, J=1.6Hz), 8.21(1H, d, J=8.8Hz), 8.02(1H, dd, J=1.6Hz, 8.8Hz), 7.76(1H, s), 7.68(1H, t, J=8.5Hz), 7.59(1H, s), # 7.54-7.51(4H, m), 7.21(1H, dd, J=2.4Hz, 12.1Hz), 7.07(1H, dd, J=2.4Hz, 8.8Hz), 5.08(2H, s), 4.11(1H, m), 3.77(2H, t, J=6.9Hz), 2.47(2H, t, J=8.0Hz), 2.40-2.10(4H, m), 2.00-1.80(4H, m), 1.70-1.60(1H, m), 1.45-1.20(3H, m) Purity >90% (NMR) MS 672(M + 1) Example No. 409 1H NMR(&dgr;) ppm 1324 300MHz, DMSO-d68.28(1H, d, J=1.5Hz), 8.20-8.85(4H, m), 7.75(1H, d, J=6.9Hz), 7.70-7.45(6H, m), 7.13(1H, dd, J=12.0Hz, 2.1Hz), 7.00(1H, dd, J=8.7Hz), 2.1Hz), 5.22(2H, s), 4.05(1H, m), 3.40-3.20(1H, m), 2.30-2.10(2H, m), 2.00-1.55(5H, m), 1.45-1.10(3H, m), 1.00(6H, d, J=6.6Hz) Purity >90% (NMR) MS 676(M + 1)

[2107] 248 TABLE 248 Example No. 410 1H NMR(&dgr;) ppm 1325 300MHz, DMSO-d6 8.31(1H, s), 8.00(1H, d, J=8.7Hz), 7.88(1H, d, J=8.7Hz), 7.70(1H, s), 7.65(1H, t, J=8.4Hz), 7.53(2H, d, J=8.4Hz), 7.49(2H, d, J=8.7Hz), 7.45-7.41(2H, m), 7.16(1H, d, J=12.0Hz), 7.04(1H, d, J=8.7Hz), 5.14(2H, s), 4.68(1H, quint, J=8.4Hz), 3.02, 2.98(6H, s), 2.30-1.85(6H, m), 1.80-1.50(2H, m) Purity >90% (NMR) MS 612(M + 1) Example No. 411 1H NMR(&dgr;) ppm 1326 300MHz, DMSO-d6 8.30(1H, s), 7.99(1H, d, J=9.0Hz), 7.87(1H, d, J=8.7Hz), 7.67(1H, s), 7.64(1H, t, J=8.7Hz), 7.53(2H, d, J=8.7Hz), 7.49(2H, d, J=7.5Hz), 7.45-7.41(2H, m), 7.15(1H, d, J=12.3Hz), 7.02(1H, d, J=8.4Hz), 5.15(2H, s), 4.67(1H, quint, J=8.7Hz), 4.02(1H, m), 3.76(1H, m), 3.55(1H, m), 3.22(2H, m), 2.40-1.20(12H, m) Purity >90% (NMR) MS 668(M + 1) Example No. 412 1H NMR(&dgr;) ppm 1327 300MHz, DMSO-d6 8.38(1H, d, J=7.5Hz), 8.33(1H, s), 8.16(1H, s), 8.02(1H, d, J=8.7Hz), 7.98(1H, d, J=9.0Hz), 7.91(1H, d, J=8.4Hz), 7.67(1H, t, # J=8.4Hz), 7.53(2H, d, J=8.7Hz), 7.48(2H, d, J=8.7Hz), 7.46(1H, d, J=8.1Hz), 7.18(1H, d, J=11.7Hz), 7.06(1H, d, J=8.7Hz), 5.13(2H, s), 4.70(1H, quint, J=8.4Hz), 4.13(1H, sept, J=6.6Hz), 2.30-1.85(6H, m), 1.80-1.50(2H, m), 1.16(6H, d, J=6.3Hz) Purity >90% (NMR) MS 626(M + 1)

[2108] 249 TABLE 249 Example No. 413 1H NMR(&dgr;) ppm 1328 300Mz, DMSO-d6 8.39(1H, d, J=7.5Hz), 8.31(1H, d, J=1.5Hz), 8.16(1H, d, J=1.9Hz), 8.06(1H, dd, J=8.8, # 1.5Hz), 7.99-7.95(2H, m), 7.76 and 7.24(4H, ABq, J=8.9Hz), 7.53 and 7.50(4H, A′B′q, J=9.1Hz), 7.46(1H, d, J=8.3Hz), 5.14(2H, s), 4.94(1H, quint, J=9.0Hz), 4.19-4.08(1H, m), 2.32-2.11(4H, brm), 2.10-1.95(2H, brm), 1.78-1.62(2H, brm), 1.26(3H, s), 1.18(3H, s) Purity >90% (NMR) MS 608(M + 1) Example No. 414 1H NMR(&dgr;) ppm 1329 300Mz, DMSO-d6 8.31(1H, d, J=1.5Hz), 8.06(1H, dd, J=8.7, 1.5Hz), 7.97(1H, d, J=8.7Hz), 7.75 and 7.22(4H, ABq, J=8.9Hz), 7.70(1H, d, J=1.9Hz), 7.53(1H, dd, J=7.9, 1.9Hz), 7.52(4H, s), 7.43(1H, d, J=7.9Hz), 5.15(2H, s), 4.93(1H, quint, J=8.9Hz), 3.01(3H, s), 2.97(3H, s), 2.32-2.11(4H, brm), 2.09-1.94(2H, brm), 1.77-1.62(2H, brm) Purity >90% (NMR) MS 594(M + 1) Example No. 415 1H NMR(&dgr;) ppm 1330 300Mz, DMSO-d6 8.31(1H, d, J=1.5Hz), 8.06(1H, dd, J=8.7, 1.5Hz), 7.98(1H, d, # J=8.7Hz), 7.75 and 7.22(4H, ABq, J=8.9Hz), 7.67(1H, d, J=1.5Hz), 7.52(4H, s), 7.49(1H, dd, J=7.9, 1.5Hz), 7.43(1H, d, J=8.9Hz), 5.16(2H, s), 4.93(1H, quint, J=8.9Hz), 3.76(1H, brs), 3.55(2H, brs), 3.22(2H, brs), 2.31-2.11(4H, brm), 2.16-1.95(2H, brm), 1.88-1.62(4H, brm), 1.48-1.28(2H, brm) Purity >90% (NMR) MS 650(M + 1)

[2109] 250 TABLE 250 Example No. 416 1H NMR(&dgr;) ppm 1331 300MHz, DMSO-d6 8.38(1H, d, J=7.7Hz), 8.30(1H, s), 8.20-7.90(4H, m), 7.72(2H, d, J=8.7Hz), 7.60-7.40(5H, m), 7.22(2H, d, J=8.7Hz), 5.13(2H, s), 4.47(1H, m), 4.15(1H, m), 2.90-2.70(4H, m), 2.60-2.30(4H, m), 1.19(6H, d, J=6.5Hz) Purity >90% (NMR) MS 640(M + 1) Example No. 417 1H NMR(&dgr;) ppm 1332 400MHz, DMSO-d6 8.33(1H, s), 8.17(1H, d, J=8.6Hz), 8.10(1H, d, J=8.6Hz), 7.82(1H, d, J=1.4Hz), 7.74(2H, d, J=8.7Hz), 7.64(1H, dd, J=8.0Hz, 1.7Hz), 7.55-7.50(4H, m), 7.43(1H, d, J=7.8Hz), 7.24(1H, d, J=8.7Hz), 5.16(2H, s), 4.49(1H, m), 3.60-3.40(4H, m), 2.90-2.70(4H, m), 2.60-2.30(4H, m), 2.20-1.80(4H, m) Purity >90% (NMR) MS 652(M + 1) Example No. 418 1H NMR(&dgr;) ppm 1333 400MHz, DMSO-d6 8.34(1H, d, J=7.6Hz), 8.25(1H, s), 8.11(1H, d, J=1.3Hz), 7.90-8.00(3H, m), 7.59(1H, t, J=8.6Hz), 7.40-7.55(5H, m), 7.12(1H, d, J=11.9Hz), 7.00(1H, d, J=8.6Hz), 5.08(2H, s), 4.30-4.10(2H, m), 2.80-2.65(4H, m), 2.45-2.30(2H, m), 1.15(6H, d, J=4.8Hz) Purity >90% (NMR) MS 658(M + 1)

[2110] 251 TABLE 251 Example No. 419 1H NMR(&dgr;) ppm 1334 400MHz, DMSO-d6 8.30(1H, s), 8.05-7.95(3H, m), 7.80-7.75(1H, m), 7.63(1H, t, J=8.6Hz), 7.55-7.35(5H, m), 7.15(1H, dd, J=12.1Hz, 2.1Hz), 7.03(1H, dd, J=8.7Hz, 2.3Hz), 5.10(2H, s), 4.23(1H, m), 3.90(2H, t, J=7.0Hz), 2.95-2.70(4H, m), 2.60-2.35(4H, m), 2.30-2.00(4H, m) Purity >90% (NMR) MS 656(M + 1) Example No. 420 1H NMR(&dgr;) ppm 1335 300Mz, DMSO-d6 8.37(1H, d, J=7.5Hz), 8.28(1H, d, J=1.5Hz), 8.17(1H, d, J=1.5Hz), 8.13(1H, d, J=8.7Hz), 7.97(1H, dd, J=8.1, 1.5Hz), 7.94(1H, dd, J=8.7, 1.5Hz), 7.61(1H, t, J=8.7Hz), 7.51 and 7.49(4H, ABq, J=8.9Hz), 7.46(1H, d, J=8.1Hz), 7.08(1H, dd, J=12.4, 2.3Hz), 6.97(1H, dd, J=8.7, 2.3Hz), 5.10(2H, s), # 4.20-4.08(1H, m), 3.62-3.56(2H, brm), 3.13-3.10(2H, brm), 1.79-1.60(3H, brm), 1.54-1.34(3H, brm), 1.21(3H, Purity >90% (NMR) MS 641(M + 1) Example No. 421 1H NMR(&dgr;) ppm 1336 300Mz, DMSO-d6 8.24(1H, d, J=1.5Hz), 8.02(1H, d, J=8.7Hz), 7.88(1H, dd, J=8.7, # 1.5Hz), 7.82(1H, d, J=1.9Hz), 7.63(1H, dd, J=7.9, 1.9Hz), 7.54(1H, t, J=8.7Hz), 7.50(4H, s), 7.42(1H, d, J=7.9Hz), 7.01(1H, dd, J=12.0, 2.3Hz), 6.91(1H, dd, J=8.7, 2.3Hz), 5.11(2H, s), 3.63-3.41(6H, m), 3.07-3.04(2H, brm), 1.95-1.79(4H, brm), 1.77-1.57(3H, brm), 1.50-1.32(3H, brm) Purity >90% (NMR) MS 653(M + 1)

[2111] 252 TABLE 252 Example No. 422 1H NMR(&dgr;) ppm 1337 300MHz, DMSO-d6 10.99(2H, s), 8.44(1H, s), 8.30(1H, s), 8.18(1H, d, J=8.7Hz), 8.14(1H, # d, J=8.7Hz), 7.98(1H, d, J=9.0Hz), 7.70-7.66(2H, m), 7.57(2H, d, J=8.7Hz), 7.54(2H, d, J=8.7Hz), 7.21(1H, d, J=12.0Hz), 7.09(1H, d, J=8.4Hz), 5.19(2H, s), 4.05(4H, s), 2.40-2.18(2H, m), 2.15-1.80(4H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 623(M + 1) Example No. 423 1H NMR(&dgr;) ppm 1338 300MHz, DMSO-d6 8.27(1H, s), 8.05(1H, d, J=8.7Hz), 7.93(1H, d, J=8.7Hz), 7.90(1H, s), 7.70(1H, d, J=8.4Hz), 7.59(1H, t, J=8.4Hz), 7.50(2H, d, # J=9.0Hz), 7.45(2H, d, J=8.7Hz), 7.41(1H, d, J=8.4Hz), 7.12(1H, d, J=12.0Hz), 7.00(1H, d, J=8.7Hz), 5.10(2H, s), 4.49(2H, t, J=7.8Hz), 4.14(2H, t, J=8.0Hz), 4.04(1H, m), 2.40-2.10(2H, m), 2.00-1.50(5H, m), 1.45-1.20(3H, m) Purity >90% (NMR) MS 640(M + 1) Example No. 424 1H NMR(&dgr;) ppm 1339 300MHz, DMSO-d6 8.30(1H, s), 8.14(1H, d, J=8.4Hz), 7.98(1H, d, J=9.3Hz), 7.89(1H, s), 7.68(1H, d, J=8.4Hz), 7.62(1H, # d, J=9.0Hz), 7.48(2H, d, J=8.4Hz), 7.43(2H, d, J=8.4Hz), 7.33(1H, d, J=8.4Hz), 7.16(1H, d, J=12.0Hz), 7.04(1H, d, J=9.0Hz), 5.07(2H, s), 4.10(1H, m), 3.92(2H, t, J=8.0Hz), 3.45(2H, t, J=8.0Hz), 2.40-2.10(2H, m), 2.00-1.50(5H, m), 1.45-1.20(3H, m) Purity >90% (NMR) MS 639(M + 1)

[2112] 253 TABLE 253 Example No. 425 1H NMR(&dgr;) ppm 1340 300MHz, DMSO-d6 9.05(1H, s), 8.30(1H, s), 8.16(1H, d, J=8.8Hz), 7.99(1H, d, J=8.6Hz), 7.72(1H, s), 7.64(1H, t, # J=8.6Hz), 7.52(1H, d, J=8.4Hz), 7.47(2H, d, J=8.7Hz), 7.42(2H, d, J=8.6Hz), 7.25(1H, d, J=8.4Hz), 7.15(1H, d, J=12.2Hz), 7.04(1H, d, J=8.6Hz), 6.60(1H, brs), 5.05(2H, s), 4.10(1H, m), 3.68(2H, t, J=6.1Hz), 3.45(2H, t, J=6.1Hz), 2.40-2.10(2H, m), 2.00-1.55(5H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 639(M + 1) Example No. 426 1H NMR(&dgr;) ppm 1341 300MHz, DMSO-d6 8.32(1H, s), 8.24(1H, d, J=8.7Hz), 8.03(1H, d, J=8.7Hz), 7.78-7.73(4H, m), 7.38-7.32(4H, m), 5.52(2H, s), 4.88(2H, s), 4.40(2H, s), 4.37(1H, m), 2.92, 2.84(6H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 643(M + 1) Example No. 427 1H NMR(&dgr;) ppm 1342 300MHz, DMSO-d6 11.26(1H, brs), 8.35(1H, s), 8.27(1H, d, J=9.0Hz), 8.05(1H, d, J=8.4Hz), 7.83-7.78(4H, m), 7.42-7.35(4H, m), 5.57(2H, s), 4.77, 4.73(2H, s), 4.37(1H, m), 3.95(1H, s), 3.70-3.00(4H, m), 2.40-1.00(14H, m) Purity >90% (NMR) MS 641(M + 1)

[2113] 254 TABLE 254 Example No. 428 1H NMR(&dgr;) ppm 1343 300MHz, DMSO-d6 8.31(1H, s), 8.26(1H, d, J=9.0Hz), 8.04(1H, d, J=8.7Hz), 7.79-7.73(4H, m), 7.38-7.31(6H, m), 5.53(2H, s), 4.90(2H, s), 4.37(1H, m), 4.05(2H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 615(M + 1) Example No. 429 1H NMR(&dgr;) ppm 1344 300MHz, DMSO-d6 8.88(1H, q, J=4.5Hz), 8.33(1H, d, J=1.5Hz), 8.18(1H, d, # J=8.7Hz), 8.01(1H, dd, J=1.5Hz, 8.7Hz), 7.89-7.83(2H, m), 7.50-7.34(3H, m), 7.20(1H, dd, J=2.1Hz, 8.4Hz), 5.61(2H, s), 4.13(1H, m), 2.84(3H, d, J=4.8Hz), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 603(M + 1) Example No. 430 1H NMR(&dgr;) ppm 1345 400MHz, DMSO-d6 8.79(1H, t, J=5.9Hz), 8.31(1H, s), 8.15(1H, d, J=8.7Hz), 7.99(1H, d, J=8.8Hz), 7.87(1H, d, J=8.1Hz), 7.85(1H, d, J=8.7Hz), 7.70(1H, t, J=8.4Hz), 7.42-7.33(3H, m), 7.18(1H, d, J=8.8Hz), 5.60(2H, s), 4.11(1H, m), 3.62-3.54(4H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 633(M + 1)

[2114] 255 TABLE 255 Example No. 431 1H NMR(&dgr;) ppm 1346 300MHz, DMSO-d6 8.31(1H, s), 8.16(1H, d, J=8.8Hz), 7.99(1H, d, J=8.7Hz), 7.74-7.60(4H, m), 7.37(2H, t, J=8.8Hz), 7.28(1H, dd, J=2.2Hz, 12.2Hz), 7.14(1H, dd, J=2.2Hz, 8.6Hz), 5.17(2H, s), 4.10(1H, m), 3.15(6H, brs), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m) Purity >90% (NMR) MS 616(M + 1) Example No. 432 1H NMR(&dgr;) ppm 1347 300MHz, DMSO-d6 8.45(1H, d, J=7.7Hz), 8.32(1H, s), 8.19(1H, d, J=8.8Hz), 8.02-7.99(2H, m), 7.70(1H, t, J=8.6Hz), # 7.60(2H, dd, J=5.4Hz, 8.7Hz), 7.37(2H, t, J=8.8Hz), 7.27(1H, dd, J=2.3Hz, 12.2Hz), 7.14(1H, dd, J=2.2Hz), 8.7Hz), 5.16(2H, s), 4.20-4.00(2H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m), 1.18(6H, d, J=6.6Hz) Purity >90% (NMR) MS 630(M + 1) Example No. 433 1H NMR(&dgr;) ppm 1348 300MHz, DMSO-d6 8.31(1H, d, J=1.4Hz), 8.15(1H, d, J=8.8Hz), 7.98(1H, dd, J=1.4Hz, 8.7Hz), 7.68-7.60(4H, m), 7.36(2H, # t, J=8.8Hz), 7.28(1H, dd, J=2.2Hz, 12.2Hz), 7.15(1H, dd, J=2.2Hz, 8.6Hz), 5.17(2H, s), 4.10(1H, m), 4.05-3.90(2H, m), 3.85-3.70(1H, m), 3.55-3.25(2H, m), 2.40-2.10(2H, m), 2.00-1.75(6H, m), 1.70-1.55(1H, m), 1.50-1.20(5H, m) Purity >90% (NMR) MS 672(M + 1)

[2115] 256 TABLE 256 Example No. 434 1H NMR(&dgr;) ppm 1349 300Mz, DMSO-d6 8.45(1H, d, J=1.5Hz), 8.26(1H, d, J=8.8Hz), 8.10(1H, dd, J=8.8, # 1.5Hz), 7.72(1H, d, J=1.5Hz), 7.64(1H, t, J=8.6Hz), 7.56-7.48(5H, m), 7.44(1H, d, J=J=7.7Hz), 7.18(1H, dd, J=12.3, 2.4Hz), 7.04(1H, dd, J=8.6, 2.4Hz), 5.15(2H, s), 4.08(1H, brt, J=11.7Hz), 3.02(3H, s), 2.99(3H, s), 2.34-2.17(2H, brm), 1.97-1.81(4H, brm), 1.70-1.60(1H, brm), 1.49-1.21(3H, brm) Purity >90% (NMR) MS 650(M + 1) Example No. 435 1H NMR(&dgr;) ppm 1350 300Mz, DMSO-d6 8.42(1H, d, J=1.5Hz), 8.24(1H, d, J=8.8Hz), 8.08(1H, dd, J=8.8, 1.5Hz), 8.00(2H, d, J=8.8Hz), 7.79(1H, # d, J=7.8Hz), 7.62(1H, t, J=8.4Hz), 7.61-7.55(3H, m), 7.44(1H, d, J=8.1Hz), 7.16(1H, dd, J=12.1, 2.6Hz), 7.02(1H, dd, J=8.4, 2.6Hz), 5.12(2H, s), 4.07(1H, brt, J=12.5Hz), 2.33(2H, brm), 1.96-1.79(4H, brm), 1.71-1.61(1H, brm), 1.49-1.21(3H, brm) Purity >90% (NMR) MS 623(M + 1) Example No. 436 1H NMR(&dgr;) ppm 1351 300MHz, DMSO-d6 8.41(1H, d, J=7.7Hz), 8.30-8.26(2H, m), 8.18(1H, d, J=1.4Hz), 7.99(1H, # dd, J=1.7Hz, 8.0Hz), 7.89(1H, d, J=10.1Hz), 7.67(1H, t, J=8.8Hz), 7.55-7.45(5H, m), 7.20(1H, d, J=12.2Hz), 7.07(1H, dd, J=2.1Hz, 8.7Hz), 5.14(2H, s), 4.18-4.11(2H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m), 1.20(6H, d, J=6.6Hz) Purity >90% (NMR) MS 680(M + 1)

[2116] 257 TABLE 257 Example No. 437 1H NMR(&dgr;) ppm 1352 Purity >90% (NMR) MS 580(M + 1) Example No. 438 1H NMR(&dgr;) ppm 1353 Purity >90% (NMR) MS 607(M + 1) Example No. 439 1H NMR(&dgr;) ppm 1354 300MHz, CDCl3 8.60(1H, d, J=1.5Hz), 8.05(1H, dd, J=1.6Hz, 8.7Hz), 7.70(1H, d, J=8.7Hz), 7.62(2H, d, J=8.2Hz), 7.49(2H, d, J=8.2Hz), 7.31(2H, d, J=8.8Hz), 7.27-7.23(2H, m), 7.06(2H, t, J=8.6Hz), 6.80(2H, d, J=8.8Hz), 5.05(2H, s), 4.38(1H, m), 3.06(6H, s), 2.45-2.20(2H, m), 2.10-1.70(5H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 591(M + 1)

[2117] 258 TABLE 258 Example No. 440 1H NMR(&dgr;) ppm 1355 300MHz, DMSO-d6 8.20(1H, s), 7.86(2H, m), 7.39(1H, d, J=7.9Hz), 7.34(1H, d, J=7.9Hz), 7.07(2H, dt, J=2.3Hz, 8.6Hz), 6.98-6.88(5H, m), 6.83(1H, d, J=8.3Hz), 5.91(1H, s), 3.96(1H, m), 2.30-1.95(2H, m), 1.90-1.50(4H, m), 1.40-1.10(3H, m) Purity >90% (NMR) MS 557(M + 1) Example No. 441 1H NMR(&dgr;) ppm 1356 300MHz, DMSO-d6 8.24(1H, d, J=1.4Hz), 8.01(1H, d, J=8.8Hz), 7.91(1H, dd, J=1.4Hz, 8.7Hz), 7.47(1H, t, J=8.4Hz), 7.43-7.35(2H, m), 7.15-7.01(5H, m), 6.92(2H, d, J=10.4Hz), 6.11(1H, s), 3.90(1H, m), 2.30-1.95(2H, m), 1.90-1.50(4H, m), 1.40-1.10(3H, m) Purity >90% (NMR) MS 557(M + 1) Example No. 442 1H NMR(&dgr;) ppm 1357 300Mz, DMSO-d6 8.26(1H, d, J=1.5Hz), 8.11(1H, d, J=8.9Hz), 7.96(1H, dd, J=8.9, 1.5Hz), 7.65-7.57(5H, m), 7.47(1H, t, J=7.7Hz), 7.35(1H, d, J=7.6Hz), 7.30-7.22(3H, m), 7.16(1H, dd, J=8.7, 2.3Hz), 6.88(1H, s), 4.04(1H, brt, J=11.3Hz), 2.98(3H, s) 2.84(3H, s), 2.30-2.10(2H, brm), 1.94-1.75(4H, brm), 1.68-1.57(1H, brm), 1.45-1.14(3H, brm) Purity >90% (NMR) MS 610(M + 1)

[2118] 259 TABLE 259 Example No. 443 1H NMR(&dgr;) ppm 1358 300Mz, DMSO-d6 8.23(1H, s), 7.98 and 7.89(2H, ABq, J=8.8Hz), 7.62-7.06(11H, m), 6.86(1H, s), 4.12-3.77(2H, brm), 3.72(1H, brs), 3.69(1H, brs), 3.18(1H, brs), 3.05(1H, brs), 2.31-2.08(2H, brm), 1.90-1.54(7H, brm), 1.48-1.13(5H, brm) Purity >90% (NMR) MS 666(M + 1) Example No. 444 1H NMR(&dgr;) ppm 1359 300MHz, DMSO-d6 8.36(1H, s), 8.00(1H, d, J=8.7Hz), 7.90(1H, d, J=9.3Hz), 7.80-7.70(2H, m), 7.63(2H, d, J=8.4H z), 7.32(2H, t, J=8.7Hz), 7.22(2H, d, J=8.4Hz), 5.62(1H, d, J=7.5Hz), 5.57(1H, brd, J=4.8Hz), 5.41(2H, s), 5.31(1H, m), 4.29(1H, m), 3.84(1H, d, J=9.0Hz), 3.50-3.20(3H, m), 2.71(3H, s), 2.40-2.20(2H, m), 1.75-1.60(1H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 718(M + 1) Example No. 445 1H NMR(&dgr;) ppm 1360 300MHz, DMSO-d6 8.36(1H, s), 8.00(1H, d, J=8.7Hz), 7.92(1H, d, J=9.3Hz), 7.57(1H, t, J=8.4Hz), 7.50-7.35(6H, m), 7.25-7.05(4H, m), 6.82(1H, s), 5.62(1H, d, J=7.2Hz), 5.56(1H, m), 5.28(1H, brs), 3.95(1H, m), 3.82(1H, d, J=8.7Hz), 3.50-3.20(3H, m), 2.30-2.05(2H, m), 1.90-1.55(5H, m), 1.40-1.10(3H, m) Purity >90% (NMR) MS 733(M + 1)

[2119] 260 TABLE 260 Example No. 446 1H NMR(&dgr;) ppm 1361 300MHz, DMSO-d6 8.29(1H, s), 8.13(1H, d, J=9.0Hz), 7.97(1H, d, J=9.0Hz), 7.63(1H, t, J=8.6Hz), 7.51-7.32(7H, m), 7.15(1H, d, J=12.0Hz), 7.03(1H, d, J=9.0Hz), 5.10(2H, s), 4.09(1H, m), 3.82(2H, t, J=6.3Hz), 3.56(2H, t, J=7.4Hz), 2.45(2H, m), 2.40-2.10(2H, m), 2.00-1.55(5H, m), 1.50-1.20(3H, m) Purity >90% (NMR) MS 674(M + 1) Example No. 702 1H NMR(&dgr;) ppm 1362 300MHz, DMSO-d6 8.97(1H, d, J=1.8Hz), 8.52(1H, d, J=2.4Hz), 8.36(1H, d, J=7.8Hz), 8.16(1H, s), 7.96(!H, d, J=8.1Hz), 7.55-7.40(5H, m),7.14(1H, d, J=12.6Hz), 7.01(1H, dd, J=8.4Hz, 1.8Hz), 5.11(2H, s), 4.20-3.95(2H, m), 2.65-2.45(2H, m), 1.95-1.80(5H, m), 1.20-1.10(3H, m) Purity >90% (NMR) MS 641(M + 1) Example No. 703 1H NMR(&dgr;) ppm 1363 300MHz, DMSO-d6 8.97(1H, d, J=1.8Hz), 8.52(1H, d, J=1.8Hz), 7.82(1H, s), 7.70-7.35(7H, m), 7.13(1H, d, J=12.3Hz), 7.00(1H, d, J=11.1Hz), 5.14(2H, s), 3.60-3.35(4H, m), 2.65-2.40(2H, m), 2.00-2.55(9H, m), 1.40-1.10(3H, m) Purity >90% (NMR) MS 653(M + 1)

[2120] Formulation Example is given in the following. This example is merely for the purpose of exemplification and does not limit the invention.

FORMULATION EXAMPLE

[2121] 261 (a) compound of Example 1 10 g (b) lactose 50 g (c) corn starch 15 g (d) sodium carboxymethylcellulose 44 g (e) magnesium stearate  1 g

[2122] The entire amounts of (a), (b) and (c) and 30 g of (d) are kneaded with water, dried in vacuo and granulated. The obtained granules are mixed with 14 g of (d) and 1 g of (e) and processed into tablets with a tableting machine to give 1000 tablets each containing 10 mg of (a).

INDUSTRIAL APPLICABILITY

[2123] As is evident from the above-mentioned results, the compound of the present invention shows a high inhibitory activity against HCV polymerase.

[2124] Therefore, the compound of the present invention can provide a pharmaceutical agent effective for the prophylaxis or treatment of hepatitis C, based on the anti-HCV effect afforded by the HCV polymerase inhibitory activity. When used concurrently with a different anti-HCV agent, such as interferon, and/or an anti-inflammatory agent and the like, it can provide a pharmaceutical agent more effective for the prophylaxis or treatment of hepatitis C. Its high inhibitory activity specific to HCV polymerase suggests the possibility of the compound being a pharmaceutical agent with slight side effects, which can be used safely for humans.

[2125] This application is based on patent application Nos. 369008/1999, 391904/2000 and 193786/2001 filed in Japan, and international application No. PCT/JP00/09181, the contents of which are hereby incorporated by reference.

Claims

1. A therapeutic agent for hepatitis C, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient:

1364

wherein

a broken line is a single bond or a double bond,

G1 is C(—R1) or a nitrogen atom,

G2 is C(—R2) or a nitrogen atom,

G3 is C(—R3) or a nitrogen atom,

G4 is C(—R4) or a nitrogen atom,

G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,

G7 is C(—R7), an oxygen atom, a sulfur atom, or a nitrogen atom optionally substituted by R8,

wherein R1, R2, R3 and R4 are each independently,

(1) hydrogen atom,

(2) C1-6 alkanoyl,

(3) carboxyl,

(4) cyano,

(5) nitro,

(6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,

group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

(7) —COORa1

wherein Ra1 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B or glucuronic acid residue,

group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH,)r—COORb1, —(CH2)r—CONRb1R2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r-SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,

(8) —CONRa2Ra3

wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

(9) —C(═NRa4) NH2

wherein Ra4 is hydrogen atom or hydroxyl group,

(10) —NHRa5

wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

(11) —ORa6

wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl(as defined above),

(12) —SO2Ra7

wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,

(13) —P((═O)(ORa31)2

wherein Ra31 is hydrogen atom, optionally substituted Cl-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

R7 and R8 are each hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

ring Cy is

(1) (C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy,

(2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or

(3)

1365

wherein u and v are each independently an integer of 1 to 3,

ring A is

(1) C6-14 aryl,

(2) C3-8 cycloalkyl,

(3) C3-8 cycloalkenyl or

(4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

R5 and R6 are each independently

(1) hydrogen atom,

(2) halogen atom,

(3) optionally substituted C1-6 alkyl (as defined above) or

(4) —ORa8

wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and

x is

(1) hydrogen atom,

(2) halogen atom,

(3) cyano,

(4) nitro,

(5) amino, C1-6 alkanoylamino,

(6) C1-6 alkylsulfonyl,

(7) optionally substituted C1-6 alkyl (as defined above),

(8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

(9) —COORa9

wherein Ra9 is hydrogen atom or C1-6 alkyl,

(10) —CONH—(CH2)1—Ra10

wherein Ra10 is optionally substituted C1-6 alkyl (as defined above), C1-6 alkoxycarbonyl or C1-6 alkanoylamino and 1 is 0 or an integer of 1 to 6,

(11) —ORa11

wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above) or

(12)

1366

 wherein

ring B is

(1′) C6-14 aryl,

(2′) C3-8 cycloalkyl or

(3′) heterocyclic group (as defined above),

each Z is independently

(1′) a group selected from the following group D,

(2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(3′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D,

wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or

(6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, as defined above,

group D:

(a) hydrogen atom,

(b) halogen atom,

(c) cyano,

(d) nitro,

(e) optionally substituted C1-6 alkyl (as defined above),

(f) —(CH2)t—CORa18,

(hereinafter each t means independently 0 or an integer of 1 to 6),

wherein Ra18 is

(1″) optionally substituted C1-6 alkyl (as defined above),

(2″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(3″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B

wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

(g) —(CH2)t—COORa19

wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(h) —(CH2)t—CONRa27Ra28

wherein Ra27 and Ra28 are each independently,

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,

(7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(9″) hydroxyl group or

(10″) C1-6 alkoxy,

(i) —(CH2)t—C(═NRa33)NH2

wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,

(j) —(CH2)t—ORa20

wherein Ra20 is

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) optionally substituted C2-6 alkenyl (as defined above),

(4″) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

(5″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(7″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(8″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(9″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

(10) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(k) —(CH2)t—O—(CH2)p—CORa21

wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,

(l) —(CH2)t—NRa22Ra23

wherein Ra22 and Ra23 are each independently

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(6″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(m) —(CH2)t—NRa29CO—Ra24

wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and Ra24 is

(1″) amino,

(2″) C1-6 alkylamino,

(3″) optionally substituted C1-6 alkyl (as defined above),

(4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(n) —(CH2)t—NRa29SO2—Ra25

wherein Ra29 is as defined above, and Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(o) —(CH2)t—S(O)q—Ra25

wherein R is as defined above, and q is 0, 1 or 2,

(p) —(CH2)t—SO2—NHRa26

wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and

(q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

w is an integer of 1 to 3, and

Y is

(1′) a single bond,

(2′) C1-6 alkylene,

(3′) C2-6 alkenylene,

(4′) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),

(5′) —CO—,

(6′) —CO2—(CH2)n—,

(7′) —CONH—(CH2)n—NH—,

(8′) —NHCO2—,

(9′) —NHCONH—,

(10′) —O—(CH2)n—CO—,

(11′) —O—(CH2)n—O—,

(12′) —SO2—,

(13′) —(CH2)m—NRa12—(CH2)n—

wherein Ra12 is

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5″) —CORb5

wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6″) —COORb5 (Rb5 is as defined above) or

(7″) —SO2Rb5 (Rb5 is as defined above),

(14′) —NRa12CO— (Ra12 is as defined above),

(15′) —CONRa13—(CH2)n—

wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(16′) —CONH—CHRa14—

wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(17′) —O—(CH2)mCRa15Ra16(CH2)n—

wherein Ra15 and Ra16 are each independently

(1″) hydrogen atom,

(2″) carboxyl,

(3″) C1-6 alkyl,

(4″) —ORb6

wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

(5) —NHRb7

wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally

(6″)

1367

wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,

(18′) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),

(19) —NRa17SO2—

wherein Ra17 is hydrogen atom or C1-6 alkyl,

(20′) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above), or

(21′) —(CH2)m—CRa15Ra16—(CH2)n— (Ra15 and Ra16 are each as defined above).

2. The therapeutic agent of claim 1, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is(are) a nitrogen atom.

3. The therapeutic agent of claim 2, wherein G2 is C(—R2) and G6 is a carbon atom.

4. The therapeutic agent of claim 2, wherein G5 is a nitrogen atom.

5. The therapeutic agent of claim 1, wherein, in formula [I], the moiety

1368

is a fused ring selected from

1369 1370

6. The therapeutic agent of claim 5, wherein, in formula [I], the moiety

1371

is a fused-ring selected from

1372

7. The therapeutic agent of claim 6, which comprises a fused ring compound of the following formula [I-1]

1373

wherein each symbol is as defined in claim 1, or a pharmaceutically acceptable salt thereof as an active ingredient.

8. The therapeutic agent of claim 6, which comprises a fused ring compound of the following formula [I-2]

1374

wherein each symbol is as defined in claim 1, or a pharmaceutically acceptable salt thereof as an active ingredient.

9. The therapeutic agent of claim 6, which comprises a fused ring compound of the following formula [I-3]

1375

wherein each symbol is as defined in claim 1, or a pharmaceutically acceptable salt thereof as an active ingredient.

10. The therapeutic agent of claim 6, which comprises a fused ring compound of the following formula [1-4]

1376

wherein each symbol is as defined in claim 1, or a pharmaceutically acceptable salt thereof as an active ingredient.

11. The therapeutic agent of claim 1, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3, —SO2Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are as defined in claim 1),

1377

12. The therapeutic agent of claim 11, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3 or —SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in claim 1.

13. The therapeutic agent of claim 1, wherein at least one of R1, R2, R3 and R4 is —COORa1 wherein Ra1 is glucuronic acid residue.

14. The therapeutic agent of claim 1, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.

15. The therapeutic agent of claim 1, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino.

16. The therapeutic agent of claim 1, wherein the ring Cy is

1378

wherein each symbol is as defined in claim 1.

17. The therapeutic agent of claim 1, wherein the ring A is C6-14 aryl.

18. The therapeutic agent of claim 1, wherein at least one substituent optionally substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy.

19. The therapeutic agent of claim 1, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— wherein each symbol is as defined in claim 1.

20. The therapeutic agent of claim 1, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D.

21. The therapeutic agent of claim 1, wherein at least one group represented by Z is a heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:

1379

wherein E1 is an oxygen atom, a sulfur atom or N(—Ra35), E2 is an oxygen atom, CH2 or N(—Ra35), E3 is an oxygen atom or a sulfur atom, wherein each Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and h′ are the same or different and each is an integer of 1 to 3.

22. The therapeutic agent of claim 21, wherein at least one-group, represented by z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D wherein said heterocyclic group is selected from the following groups:

1380

wherein each symbol is as defined in claim 21.

23. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in claim 1, and at least one of Ra27 and Ra27 is C1-6 alkoxy.

24. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in claim 1, and Ra3 is hydroxyl group or C1-6 alkoxy.

25. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—O—(CH2)p—CORa21, wherein each symbol is as defined in claim 1, and Ra21 is amino.

26. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in claim 1, and Ra24 is amino or C1-6 alkylamino.

27. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in claim 1, and at lease one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B.

28. The therapeutic agent of claim 1, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.

29. The therapeutic agent of claim 1, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient:

1381

wherein

a broken line is a single bond or a double bond,

G1 is C(—R1) or a nitrogen atom,

G2 is C(—R2) or a nitrogen atom,

G3 is C(—R3) or a nitrogen atom,

G4 is C(—R4) or a nitrogen atom,

G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,

G7 is C(—R7), an oxygen atom, sulfur atom, or a nitrogen atom optionally substituted by R8,

wherein R1, R2, R3 and R4 are each independently,

(1) hydrogen atom,

(2) C1-6 alkanoyl,

(3) carboxyl,

(4) cyano,

(5) nitro,

(6) C1-6 alkyl optionally substituted by 1 to 3 substitutent(s) selected from the following group A,

group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

(7) —COORa1

wherein Ra1 is optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B,

group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,

(8) —CONRa2Ra3

wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

(9) —C(═NRa4)NH2

wherein Ra4 is hydrogen atom or hydroxyl group,

(10) —NHRa5

wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

(11) —ORa6

wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

(12) —SO2Ra7

wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino or

(13) —P(═O)(ORa31)2

wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, and

R7 and R8 are each hydrogen atom or optionally substituted C1-6 alkyl(as defined above),

ring Cy is

(1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy,

(2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or

(3)

1382

wherein u and v are each independently an integer of 1 to 3,

ring A is

(1) C6-14 aryl,

(2) C3-8 cycloalkyl,

(3) C3-8 cycloalkenyl or

(4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

R5 and R6 are each independently

(1) hydrogen atom,

(2) halogen atom,

(3) optionally substituted C1-6 alkyl (as defined above) or

(4) —ORa8

wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and

x is

(1) hydrogen atom,

(2) halogen atom,

(3) cyano,

(4) nitro,

(5) amino, C1-6 alkanoylamino,

(6) C1-6 alkylsulfonyl,

(7) optionally substituted C1-6 alkyl (as defined above),

(8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

(9) —COOR9a

wherein Ra9 is hydrogen atom or C1-6 alkyl,

(10) —CONH—(CH2)lRa10

wherein Ra10 is optionally substituted C1-6 alkyl (as defined above), C1-6 alkoxycarbonyl or C1-6 alkanoylamino and 1 is 0 or an integer of 1 to 6,

(11) —ORa11

wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above) or

(12)

1383

 wherein

ring B is

(1′) C6-14 aryl,

(2′) C3-8 cycloalkyl or

(3′) heterocyclic group (as defined above),

each Z is independently

(1′) a group selected from the following group D,

(2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(3′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(4′) C6-4 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D or

(5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D

wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

group D:

(a) hydrogen atom,

(b) halogen atom,

(c) cyano,

(d) nitro,

(e) optionally substituted C1-6 alkyl (as defined above),

(f) —(CH2)t—CORa18, (hereinafter each t means independently 0 or an integer of 1 to 6),

wherein Ra18 is

(1″) optionally substituted C1-6 alkyl (as defined above),

(2″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(3″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

(g) —(CH2)t—COORa19

wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(h) —(CH2)t—CONRa27Ra28

wherein Ra27 and Ra28 are each independently,

(1′) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B

(4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,

(7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

(8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(i) —(CH2)t—C(═NRa33)NH2

wherein Ra33 is hydrogen atom or C1-6 alkyl,

(j) —(CH2)t—ORa20

wherein Ra20 is

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) optionally substituted C2-6 alkenyl (as defined above),

(4″) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

(5″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(7″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(8″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(9″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

(10″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(k) —(CH2)t—O—(CH2)p—CORa21

wherein Ra21 is C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

and p is 0 or an integer of 1 to 6,

(l) —(CH2)t—NRa22Ra23

wherein Ra22 and Ra23 are each independently

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(5″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(m) —(CH2)t—NRa29CO—Ra24

wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, Ra24 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(n) —(CH2)t—NHSO2—Ra25

wherein Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(o) —(CH2)t—S(O)q—Ra25

wherein Ra25 is as defined above, and q is 0, 1 or 2, and

(p) —(CH2)t—SO2—NHRa26 wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

w is an integer of 1 to 3, and

Y is

(1′) a single bond,

(2′) C1-6 alkylene,

(3′) C2-6 alkenylene,

(4′) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),

(5′) —CO—,

(6′) —CO2—(CH2)n—,

(7′) —CONH—(CH2)n—NH—,

(8′) —NHCO2—,

(9′) —NHCONH—,

(10′) —O—(CH2)n—CO—,

(11′) —O—(CH2)n—O—,

(12′) —SO2—,

(13′) —(CH2)m—NRa12—(CH2)n—

wherein Ra12 is

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5″) —CORb5

wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6″) —COORb5 (Rb5 is as defined above) or

(7″) —SO2Rb5 (Rb5 is as defined above),

(14′) —NRa12CO— (Ra12 is as defined above),

(15′) —CONRa13—(CH2)n—

wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(16′) —CONH—CHRa14—

wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(17′) —O—(CH2)m—CRa15Ra16—(CH2)n—

wherein Ra15 and Ra16 are each independently

(1″) hydrogen atom,

(2″) carboxyl,

(3″) C1-6 alkyl,

(4″) —ORb6

wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

(5″) —NHRb7

wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or

Ra15 is optionally

(6″)

1384

wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,

(18′) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),

(19′) —NRa17SO2—

wherein Ra17 is hydrogen atom or C1-6 alkyl or

(20′) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2,

Ra15 and Ra16 are each as defined above).

30. The therapeutic agent of claim 29, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is(are) a nitrogen atom.

31. The therapeutic agent of claim 30, wherein G2 is C(—R2) and G6 is a carbon atom.

32. The therapeutic agent of claim 30, wherein G5 is a nitrogen atom.

33. The therapeutic agent of claim 29, wherein, in formula [I], the moiety

1385

is a fused ring selected from

1386 1387

34. The therapeutic agent of claim 33, wherein, in formula [I], the moiety

1388

is a fused ring selected from

1389

35. The therapeutic agent of claim 34, which comprises a fused ring compound of the following formula [I-1]

1390

wherein each symbol is as defined in claim 29,

or a pharmaceutically acceptable salt thereof as an active ingredient.

36. The therapeutic agent of claim 34, which comprises a fused ring compound of the following formula [I-2]

1391

wherein each symbol is as defined in claim 29,

or a pharmaceutically acceptable salt thereof as an active ingredient.

37. The therapeutic agent of claim 34, which comprises a fused ring compound of the following formula [I-3]

1392

wherein each symbol is as defined in claim 29,

or a pharmaceutically acceptable salt thereof as an active ingredient.

38. The therapeutic agent of claim 34, which comprises a fused ring compound of the following formula [I-4]

1393

wherein each symbol is as defined in claim 29,

or a pharmaceutically acceptable salt thereof as an active ingredient.

39. The therapeutic agent of claim 29, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3 or —SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in claim 29.

40. The therapeutic agent of claim 29, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl.

41. The therapeutic agent of claim 29, wherein the ring A is C6-14 aryl.

42. A fused ring compound of the following formula [II]

1394

wherein

the moiety

1395

 is a fused ring selected from

1396

wherein R1, R2, R3 and R4 are each independently,

(1) hydrogen atom,

(2) C1-6 alkanoyl,

(3) carboxyl,

(4) cyano,

(5) nitro,

(6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,

group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

(7) —COORa1

wherein Ra1 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B or glucuronic acid residue,

group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,

(8) —CONRa2Ra3

wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

(9) —C(═NRa4)NH2

wherein Ra4 is hydrogen atom or hydroxyl group,

(10) —NHRa5

wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

(11) —ORa6

wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

(12) —SO2Ra7

wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,

(13) —P(═O)(ORa31)2

wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

(14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

R7 is hydrogen atom or optionally substitute C1-6 alkyl (as defined above),

ring Cy′ is

(1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy, or (2)

1397

wherein u and v are each independently an integer of 1 to 3,

ring A′ is a group selected from a group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,

R5′ and R6′ are each independently

(1) hydrogen atom,

(2) halogen atom,

(3) optionally substituted C1-6 alkyl (as defined above) or

(4) hydroxyl group

ring B is

(1) C6-14 aryl,

(2) C3-8 cycloalkyl or

(3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

each Z is independently

(1) a group selected from the following group D,

(2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(5) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or

(6) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, as defined above,

group D:

(a) hydrogen atom,

(b) halogen atom,

(c) cyano,

(d) nitro,

(e) optionally substituted C1-6 alkyl (as defined above),

(f) —(CH2)t—CORa18, (hereinafter each t means independently 0 or an integer of 1 to 6),

wherein Ra18 is

(1′) optionally substituted C1-6 alkyl (as defined above),

(2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(3′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

(g) —(CH2)t—COORa19

wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(h) —(CH2)t—CONRa27Ra28

wherein Ra27 and Ra28 are each independently,

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,

(7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(9″) hydroxyl group or

(10″) C1-6 alkoxy,

(i) —(CH2)t—C(═NRa33)NH2

wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,

(j) —(CH2)t—ORa20

wherein Ra20 is

(1′) hydrogen atom,

(2′) optionally substituted C1-6 alkyl (as defined above),

(3′) optionally substituted C2-6 alkenyl (as defined above),

(4′) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

(5′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(7′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(8′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(9′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

(10′) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(k) —(CH2)t—O—(CH2)p—CORa21

wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

and p is 0 or an integer of 1 to 6,

(l) —(CH2)t—NRa22Ra23

wherein Ra22 and Ra23 are each independently

(1′) hydrogen atom,

(2′) optionally substituted C1-6 alkyl (as defined above),

(3′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(6′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(m) —(CH2)t—NRa29CO—Ra24

wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and

Ra24 is

(1′) amino,

(2′) C1-6 alkylamino,

(3′) optionally substituted C1-6 alkyl (as defined above),

(4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

(6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(n) —(CH2)t—NRa29SO2—Ra25

wherein Ra29 is as defined above, and Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(o) —(CH2)t—S(O)q—Ra25

wherein Ra25 is as defined above, and q is 0, 1 or 2,

(p) —(CH2)t—SO2—NHRa26

wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and

(q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

w is an integer of 1 to 3, and

Y is

(1) a single bond,

(2) C1-6 alkylene,

(3) C2-6 alkenylene,

(4) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),

(5) —CO—,

(6) —CO2—(CH2)n—,

(7) —CONH—(CH2)n—NH—,

(8) —NHCO2—,

(9) —NHCONH—,

(10) —O—(CH2)n—CO—,

(11) —O—(CH2)n—O—,

(12) —SO2—,

(13) —(CH2)m—NRa12—(CH2)n—

wherein Ra12 is

(1′) hydrogen atom,

(2′) optionally substituted C1-6 alkyl (as defined above),

(3′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5′) —CORb5

wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6′) —COORb5 (Rb5 is as defined above) or

(7′) —SO2Rb5 (Rb5 is as defined above),

(14) —NRa12CO— (Ra12 is as defined above),

(15) —CONRa13—(CH2)n—

wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(16) —CONH—CHRa14—

wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(17) —O—(CH2)m—CRa15Ra16—(CH2)n—

wherein Ra15 and Ra16 are each independently

(1′) hydrogen atom,

(2′) carboxyl,

(3′) C1-6 alkyl,

(4′) —ORb6

wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

(5′) —NHRb7

wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally

(6′)

1398

wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,

(18) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),

(19) —NRa17SO2—

wherein Ra17 is hydrogen atom or C1-6 alkyl,

(20) —S(O)e—(CH2)mCRa15Ra16—(CH2)n— (e is 0, 1 or 2,

Ra15 and Ra16 are each as defined above), or

(21) —(CH2)m—CRa15Ra16—(CH2)n— (Ra15 and Ra16 are each as defined above),

or a pharmaceutically acceptable salt thereof.

43. The fused ring compound of claim 42, which is represented by the following formula [II-1]

1399

wherein each symbol is as defined in claim 42,

or a pharmaceutically acceptable salt thereof.

44. The fused ring compound of claim 42, which is represented by the following formula [II-2]

1400

wherein each symbol is as defined in claim 42,

or a pharmaceutically acceptable salt thereof.

45. The fused ring compound of claim 42, which is represented by the following formula [II-3]

1401

wherein each symbol is as defined in claim 42,

or a pharmaceutically acceptable salt thereof.

46. The fused ring compound of claim 42, which is represented by the following formula [II-4]

1402

wherein each symbol is as defined in claim 42,

or a pharmaceutically acceptable salt thereof.

47. The fused ring compound of claim 42, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3, —SO2 Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are as defined in claim 42),

1403

or a pharmaceutically acceptable salt thereof.

48. The fused ring compound of claim 47, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in claim 42, or a pharmaceutically acceptable salt thereof.

49. The fused ring compound of claim 48, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in claim 42, or a pharmaceutically acceptable salt thereof.

50. The fused ring compound of claim 49, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.

51. The fused ring compound of claim 42, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is glucuronic acid residue, or a pharmaceutically acceptable salt thereof.

52. The fused ring compound of claim 42, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.

53. The fused ring compound of claim 42, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.

54. The fused ring compound of claim 42, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.

55. The fused ring compound of claim 42, wherein the ring Cy′ is

1404

wherein each symbol is as defined in claim 42, or a pharmaceutically acceptable salt thereof.

56. The fused ring compound of claim 42, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.

57. The fused ring compound of claim 56, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.

58. The fused ring compound of claim 57, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

59. The fused ring compound of claim 42, wherein at least one substituent optionaly substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.

60. The fused ring compound of claim 42, wherein the Y is —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (wherein each symbol is as defined in claim 42), or a pharmaceutically acceptable salt thereof.

61. The fused ring compound of claim 42, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in claim 42), or a pharmaceutically acceptable salt thereof.

62. The fused ring compound of claim 61, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in claim 42, or a pharmaceutically acceptable salt thereof.

63. The fused ring compound of claim 42, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in claim 42), or a pharmaceutically acceptable salt thereof.

64. The fused ring compound of claim 42, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

65. The fused ring compound of claim 42, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D, or a pharmaceutically acceptable salt thereof.

66. The fused ring compound of claim 42, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:

1405

wherein E1 is an oxygen atom, a sulfur atom or N(—Ra35), E2 is an oxygen atom, CH2 or N(—Ra35), E3 is an oxygen atom or a sulfur atom, wherein each Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and h′ are the same or different and each is an integer of 1 to 3, or a pharmaceutically acceptable salt thereof.

67. The fused ring compound of claim 66, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:

1406

wherein each symbol is as defined in claim 66, or a pharmaceutically acceptable salt thereof.

68. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in claim 42, and at least one of Ra27 and Ra28 is C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.

69. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in claim 42, and Ra33 is hydroxyl group or C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.

70. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—(CH2)p—CORa21 wherein each symbol is as defined in claim 42, and Ra21 is amino, or a pharmaceutically acceptable salt thereof.

71. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in claim 42, and Ra24 is amino or C1-6 alkylamino, or a pharmaceutically acceptable salt thereof.

72. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in claim 42, and at least one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B, or a pharmaceutically acceptable salt thereof.

73. The fused ring compound of claim 42, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.

74. The fused ring compound of claim 42, which is represented by the following formula [II]

1407

wherein

the moiety

1408

 is a fused ring selected from

1409

wherein R1, R2, R3 and R4 are each independently,

(1) hydrogen atom,

(2) C1-6 alkanoyl,

(3) carboxyl,

(4) cyano,

(5) nitro,

(6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,

group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

(7) —COORa1

wherein Ra1 is optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B,

group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2

wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,

(8) —CONRa2Ra3

wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

(9) —C(═NRa4)NH2

wherein Ra4 is hydrogen atom or hydroxyl group,

(10) —NHRa5

wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

(11) —ORa6

wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

(12) —SO2Ra7

wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino or

(13) —P(═O)(ORa31)2

wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, and

R7 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

ring Cy′ is

(1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy, or

(2)

1410

wherein u and v are each independently an integer of 1 to 3,

ring A′ is a group selected from a group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,

R5′ and R6′ are each independently

(1) hydrogen atom,

(2) halogen atom,

(3) optionally substituted C1-6 alkyl (as defined above) or

(4) hydroxyl group

ring B is

(1) C6-14 aryl,

(2) C3-8 cycloalkyl or

(3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

each Z is independently

(1) a group selected from the following group D,

(2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

(4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D or

(5) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

group D:

(a) hydrogen atom,

(b) halogen atom,

(c) cyano,

(d) nitro,

(e) optionally substituted C1-6 alkyl (as defined above),

(f) —(CH2)tCORa18, (hereinafter each t means independently 0 or an integer of 1 to 6),

wherein Ra18 is

(1′) optionally substituted C1-6 alkyl (as defined above),

(2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(3′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B

wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

(g) —(CH2)t—COORa19

wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(h) —(CH2)t—CONRa27Ra28

wherein Ra27 and Ra28 are each independently,

(1″) hydrogen atom,

(2″) optionally substituted C1-6 alkyl (as defined above),

(3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,

(7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

(8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(i) —(CH2)t—C(═NRa33)NH2

wherein Ra33 is hydrogen atom or C1-6 alkyl,

(j) —(CH2)tORa20

wherein Ra20 is

(1′) hydrogen atom,

(2′) optionally substituted C1-6 alkyl (as defined above),

(3′) optionally substituted C2-6 alkenyl (as defined above),

(4′) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

(5′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(7′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(8′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(9′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

(10′) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(k) —(CH2)t—O—(CH2)p—CORa21

wherein Ra21 is C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

and p is 0 or an integer of 1 to 6,

(1) —(CH2)t—NRa22Ra23

wherein Ra22 and Ra23 are each independently

(1′) hydrogen atom,

(2′) optionally substituted C1-6 alkyl (as defined above),

(3′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

(5′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(m) —(CH2)t—NRa29CO—Ra24

wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, Ra24 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(n) —(CH2)t—NHSO2Ra25

wherein Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B

or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(o) —(CH2)t—S(O)q—Ra25

wherein Ra25 is as defined above, and q is 0, 1 or 2, and

(p) —(CH2)t—SO2—NHRa26

wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B

or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

w is an integer of 1 to 3, and

Y is

(1) a single bond,

(2) C1-6 alkylene,

(3) C2-6 alkenylene,

(4) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),

(5) —CO—,

(6) —CO2—(CH2)n—,

(7) —CONH—(CH2)n—NH—,

(8) —NHCO2—,

(9) —NHCONH—,

(10) —O—(CH2)n—CO—,

(11) —O—(CH2)n—O—,

(12) —SO2—,

(13) —(CH2)m—NRa12—(CH2)n—

wherein Ra12 is

(1′) hydrogen atom,

(2′) optionally substituted C1-6 alkyl (as defined above),

(3′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(5′) —CORb5

wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(6′) —COORb5 (Rb5 is as defined above) or

(7′) —SO2Rb5 (Rb5 is as defined above),

(14) —NRa12CO— (Rb12 is as defined above),

(15) CONRa13—(CH2)n—

wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(16) —CONH—CHRa14—

wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

(17) —O—(CH2)m—CRa15Ra16—(CH2)n—

wherein Ra15 and Ra16 are each independently

(1′) hydrogen atom,

(2′) carboxyl,

(3′) C1-6 alkyl,

(4′) —ORb6

wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

(5′) —NHRb7

wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally

(6′)

1411

wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,

(18) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),

(19) —NRa17SO2—

wherein Ra17 is hydrogen atom or C1-6 alkyl or

(20) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2,

Ra15 and Ra16 are each as defined above),

or a pharmaceutically acceptable salt thereof.

75. The fused ring compound of claim 74, which is represented by the following formula [II-1]

1412

wherein each symbol is as defined in claim 74,

or a pharmaceutically acceptable salt thereof.

76. The fused ring compound of claim 74, which is represented by the following formula [II-2]

1413

wherein each symbol is as defined in claim 74,

or a pharmaceutically acceptable salt thereof.

77. The fused ring compound of claim 74, which is represented by the following formula [II-3]

1414

wherein each symbol is as defined in claim 74,

or a pharmaceutically acceptable salt thereof.

78. The fused ring compound of claim 74, which is represented by the following formula [II-4]

1415

wherein each symbol is as defined in claim 74

or a pharmaceutically acceptable salt thereof.

79. The fused ring compound of claim 74, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in claim 74, or a pharmaceutically acceptable salt thereof.

80. The fused ring compound of claim 79, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in claim 74, or a pharmaceutically acceptable salt thereof.

81. The fused ring compound of claim 80, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.

82. The fused ring compound of claim 74, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.

83. The fused ring compound of claim 82, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.

84. The fused ring compound of claim 74, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.

85. The fused ring compound of claim 74, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.

86. The fused ring compound of claim 85, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

87. The fused ring compound of claim 74, wherein the Y is —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (wherein each symbol is as defined in claim 74), or a pharmaceutically acceptable salt thereof.

88. The fused ring compound of claim 87, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in claim 74), or a pharmaceutically acceptable salt thereof.

89. The fused ring compound of claim 88, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in claim 74, or a pharmaceutically acceptable salt thereof.

90. The fused ring compound of claim 74, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

91. The fused ring compound of claim 42 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of

ethyl 2-[4-(3—bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate,

2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate,

ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate,

ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylate,

1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylic acid,

2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid,

2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide,

2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole,

2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime,

ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate,

1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid,

ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

2-{4[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate,

2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid,

ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylate,

ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate,

ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylate,

1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylic acid,

2-(benzyloxyphenyl)-1-cyclopentylbenzimidazole, ethyl 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylate,

2-(4-benzyloxyphenyl)-1-cyclopentyl-N,N-dimethylbenzimidazole-5-carboxamide,

2-(4-benzyloxyphenyl)-1-cyclopentyl-N-methoxy-N-methylbenzimidazole-5-carboxamide,

2-(4-benzyloxyphenyl)-1-cyclopentyl-5-(1-hydroxy-1-methylethyl)-benzimidazole,

5-acetyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole,

2-(4-benzyloxyphenyl)-1-cyclopentyl-N-(2-dimethylaminoethyl)-benzimidazole-5-carboxamide dihydrochloride,

2-(4-benzyloxyphenyl)-1-cyclopentyl-5-nitrobenzimidazole,

5-amino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole hydrochloride,

5-acetylamino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole,

2-(4-benzyloxyphenyl)-1-cyclopentyl-5-methanesulfonyl-aminobenzimidazole,

5-sulfamoyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole,

2-[4-(4-tert-butylbenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid,

2-[4-(4-carboxybenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid,

2-[4-(4-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid,

2-{4-[(2-chloro-5-thienyl)methoxy]phenyl}-1-cyclopentyl-benzimidazole-5-carboxylic acid,

1-cyclopentyl-2-[4-(4-trifluoromethylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid,

1-cyclopentyl-2-[4-(4-methoxybenzyloxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclopentyl-2-[4-(4-pyridylmethoxy)phenyl]benzimidazole-5-carboxylic acid hydrochloride,

1-cyclopentyl-2-[4-(4-methylbenzyloxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclopentyl-2-{4-[(3,5-dimethyl-4-isoxazolyl)methoxy]phenyl}-benzimidazole-5-carboxylic acid,

[2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazol-5-yl]-carbonylaminoacetic acid,

2-[4-(2-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid,

2-[4-(3-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid,

2-(4-benzyloxyphenyl)-3-cyclopentylbenzimidazole-5-carboxylic acid,

2-[4-(benzenesulfonylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid,

1-cyclopentyl-2-[4-(3,5-dichlorophenylcarbonylamino)phenyl]-benzimidazole-5-carboxylic acid,

2-{4-[(4-chlorophenyl)carbonylamino]phenyl}-1-cyclopentyl-benzimidazole-5-carboxylic acid,

2-{4-[(4-tert-butylphenyl)carbonylamino]phenyl}-1-cyclopentyl-benzimidazole-5-carboxylic acid,

2-{4-[(4-benzyloxyphenyl)carbonylamino]phenyl}-1-cyclopentyl-benzimidazole-5-carboxylic acid,

trans-4-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]cyclohexan-1-ol,

trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-methoxycyclohexane,

2-(4-benzyloxyphenyl)-5-carboxymethyl-1-cyclopentylbenzimidazole,

2-[(4-cyclohexylphenyl)carbonylamino]-1-cyclopentylbenzimidazole-5-carboxylic acid,

1-cyclopentyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclopentyl-2-[4-(3,4-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclopentyl-2-[4-(phenylcarbamoylamino)phenyl]benzimidazole-5-carboxylic acid,

1-cyclopentyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclopentyl-2-(4-phenethyloxyphenyl)benzimidazole-5-carboxylic acid,

trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-tert-butylcyclohexane,

2-(4-benzyloxyphenyl)-5-carboxymethoxy-1-cyclopentylbenzimidazole,

2-(4-benzylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid,

2-[4-(N-benzenesulfonyl-N-methylamino)phenyl]-1-cyclopentyl-benzimidazole-5-carboxylic acid,

2-[4-(N-benzyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-(4-phenethylphenyl)benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3,5-di-tert-butylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid,

2-(4-benzyloxyphenyl)-1-(4-methylcyclohexyl)benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(2-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(1-naphthyl)methoxyphenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(dibenzylamino)phenyl]benzimidazole-5-carboxylic acid,

2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-(4-benzyloxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(dibenzylmethoxy)phenyl]benzimidazole-5-carboxylic acid,

2-(4-benzoylmethoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3,3-diphenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid,

2-[4-(3-chloro-6-phenylbenzyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(phenoxy)ethoxy]phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3-phenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(5-phenylpentyloxy)phenyl]benzimidazole-5-carboxylic acid,

2-(2-benzyloxy-5-pyridyl)-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(3,4,5-trimethoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid,

2-(4-benzyloxyphenyl)-1-(4,4-dimethylcyclohexyl)benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(1-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid,

2-[4-(2-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-[4-(3-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(2-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(2-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(2-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(2-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethoxy]phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(4-trifluoromethylphenyl)benzyloxy]-phenyl}benzimidazole-5-carboxylic acid,

2-{4-[bis(4-chlorophenyl)methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(4-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(2-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(3-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid,

2-(4-benzyloxyphenyl)-1-cycloheptylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(2-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(2,2-diphenylethoxy)phenyl]benzimidazole-5-carboxylic acid,

cis-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-fluorocyclohexane,

1-cyclohexyl-2-[4-(2-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid,

2-{4-[(2R)-2-benzyloxycarbonylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{2-fluoro-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid,

2-[4-(4-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[bis(4-methylphenyl)methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[bis(4-fluorophenyl)methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-6-methoxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid,

1-cyclohexyl-6-hydroxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid,

1-cyclohexyl-6-methyl-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid,

2-{4-[2-(2-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[2-(3-benzyloxyphenyl)ethoxy]phenyl-}1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-[4-(2-carboxymethyloxyphenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-[4-(3-carboxymethyloxyphenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(4-methylphenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(4-methoxyphenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxlic acid,

1-cyclohexyl-2-{2-methyl-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid,

2-{4-[2-(4-tert-butylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-(3-chloro-6-phenylbenzyloxy)-2-fluorophenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(3,5-dichlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[bis(4-fluorophenyl)methoxy]-2-fluorophenyl}1-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-(4-benzyloxyphenoxy)-2-chlorophenyl-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-(4-benzyloxyphenoxy)-2-trifluoromethylphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(2-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[(2R)-2-amino-2-phenylethoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-[4-(2-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-[4-(3-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[3-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(3,4,5-trimethoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(2-biphenylyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride,

1-cyclohexyl-2-{4-[3-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride,

2-{4-[(2R)-2-acetylamino-2-phenylethoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(4-methyl-3-pentenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(3-methyl-3-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

2-{4-[{(2S)-1-benzyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[3-chloro-6-(4-methylthiophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(4-methanesulfonylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(2-thienyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(3-chlorophenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-[4-(4-benzyloxyphenoxy)-3-fluorophenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[3-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(2-propynyloxy)phenoxy]phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(3-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

2-(4-benzyloxy-2-methoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-[4-(carboxydiphenylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-nitrobenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-acetylamino-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

2-{4-[{(2S)-1-benzyloxycarbonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{2-chloro-4-[2-(4-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(2-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-fluorobenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-carboxy-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(dimethylcarbamoylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(piperidinocarbonylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

2-{4-[{(2S)-1-benzenesulfonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[{(2S)-1-benzoyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-carbamoylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(dimethylcarbamoylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(piperidinocarbonylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-{(1-methanesulfonyl-4-piperidyl)methoxy}-phenoxy]phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[{2-methyl-5-(4-chlorophenyl)-4-oxazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid,

2-{4-[3-(3-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-(4-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(4-fluorobenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[{(2S)-1-(4-nitrophenyl)-2-pyrrolidinyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[{(2S)-1-phenyl-2-pyrrolidinyl}methoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{(2S)-1-(4-acetylaminophenyl)-2-pyrrolidinyl}methoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[{5-(4-chlorophenyl)-2-methyl-4-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[bis(3-fluorophenyl)methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[2-(4-chlorophenyl)-3-nitrobenzyloxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(4-tetrahydropyranyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(4-trifluoromethylbenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(1-methyl-4-piperidyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid,

2-{4-[3-(4-tert-butylbenzyloxy)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-(2-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(3-pyridyl)phenoxy]phenyl}benzimidazole-5-carboxylic acid,

2-{4-[3-(4-chlorophenyl)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(4-methoxyphenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[{4-(4-methanesulfonylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid,

2-{4-[{4-(4-chlorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[1-(4-chlorobenzyl)-3-piperidyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-{(2-methyl-4-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-{(2,4-dimethyl-5-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[3-(3,5-dichlorophenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid,

2-{4-[1-(4-chlorobenzyl)-4-piperidyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[4-carbamoyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[4-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[3-{(2-chloro-4-pyridyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[{(2S)-1-(4-dimethylcarbamoylphenyl)-2-pyrrolidinyl}-methoxy]phenyl}1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-ethoxycarbonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-[4-(3-trifluoromethylphenoxy)phenyl]-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[{4-(4-dimethylcarbamoylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboloxylic acid,

2-{4-[{4-(4-chlorophenyl)-2-methyl-5-pyrimidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{2-(4-chlorophenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[{3-(4-chlorophenyl)-2-pyridyl}methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[2-(3-chlorophenyl)-4-methylamino-1,3,5-triazin-6-yloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate,

2-{4-[2-(4-chlorophenyl)-4-(5-tetrazolyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-[4-(4-benzyloxy-6-pyrimidinyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[4-(4-pyridylmethoxy)-6-pyrimidinyloxy]phenyl}-benzimidazole-5-carboxylic acid,

2-{4-[4-(3-chlorophenyl)-6-pyrimidinyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate,

methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl) benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride,

methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[3-(tert-butylsulfamoyl)-6-(4-chlorophenyl) benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-sulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate,

2-(4-benzyloxycyclohexyl)-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-[2-(2-biphenylyloxymethyl)-5-thienyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-[2-(2-biphenylyloxymethyl)-5-furyl]1-cyclohexylbenzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-hydroxymethyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid,

1-cyclohexyl-2-{4-[{4-(4-carboxyphenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride,

1-cyclohexyl-2-{2-fluoro-4-[4-fluoro-2-(3-fluorobenzoyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-sulfonic acid,

2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-benzimidazole-4-carboxylic acid,

1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-5-(4-pyridylmethoxy)-phenoxy]phenyl}benzimidazole-5-carboxylic acid dihydrochloride,

1-cyclohexyl-2-{4-[3-carboxy-5-(4-pyridylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-4-carboxylic acid,

2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{2-(4-carboxyphenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-trifluoromethyl-phenyl) benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride,

1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-methylthiophenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-2-fluorophenyl}1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]-2-fluorophenyl}1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[3-dimethylcarbamoyl-6-(4-methanesulfonylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[3-dimethylcarbamoyl-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[3-dimethylcarbamoyl-6-(4-dimethylcarbamoylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-dimethylsulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-methanesulfonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-dimethylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-methanesulfonylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-diethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-isopropylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-piperidinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(1-pyrrolidinyl)carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethyl)carbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidino)-carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-morpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-thiomorpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[3-(carboxymethylcarbamoyl)-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-{4-(2-carboxyethyl)phenyl}-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[3-chloro-6-(4-hydroxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[3-chloro-6-(4-methoxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(3-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-methylthiobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-methylsulfinylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-cyanobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[bis(3-pyridyl)methoxy]-2-fluorophenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[bis(4-dimethylcarbamoylphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

sodium 2-{4-[2-thienyl-3-thienylmethoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

methyl 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

sodium 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-carboxyphenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-carbamoylphenyl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[5-amino-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid,

2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-methoxybenzylthio]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[bis(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-[4-(phenyl-3-pyridylmethoxy)-2-fluorophenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid,

methyl 2-{4-[2-(4-chlorophenyl)-5-(methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate,

2-{4-[5-chloro-2-(4-pyridyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(benzylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(cyclohexylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-4-[2-(4-chlorophenyl)-5-(4-pyridylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(N-benzyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic acid,

2-(4-benzyloxyphenyl)-1-cyclopentyl-1H-indole-5-carboxylic acid,

ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate,

2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid, and

2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid.

92. The fused ring compound of claim 42 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of

2-{4-[5-dimethylaminocarbonyl-2-(4-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperazin-1-ylcarbonyl) benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{N-(3-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{N-(2-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(cyclohexylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2-pyridin-4-ylethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[(4-fluorophenyl){4-(dimethylaminocarbonyl)phenyl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[(4-fluorophenyl)(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, and

2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride.

93. The fused ring compound of claim 42 or a pharmaceutically acceptable salt thereof, which is selected from the group, consisting of

methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate,

methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate,

methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate,

methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate,

2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{(4-hydroxypiperidin-1-ylcarbonyl)methoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-4-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[5-(2-aminothiazol 4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl)ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadiazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{(ethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-{(isopropylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-{4-(methylthio)phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-{4-(methylthio)phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid,

2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-44-(2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride,

2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-yl carbonyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole,

2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzimidazole hydrochloride,

2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole,

2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole,

2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}methyl]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid,

2-{4-[(3-dimethylcarbamoylphenyl)(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[{3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-&bgr;-D-glucuronic acid,

{[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-&bgr;-D-glucuronic acid,

2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride,

2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride, and

2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride.

94. A pharmaceutical composition comprising a fused ring compound of claim 42, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

95. A hepatitis C virus polymerase inhibitor comprising a fused ring compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

96. An anti-hepatitis C virus agent comprising a fused ring compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

97. A therapeutic agent for hepatitis C comprising a fused ring compound of claim 42, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

98. An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of claim 96 and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.

99. An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of claim 96 and (b) interferon.

100. A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of claim 95 and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.

101. A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of claim 95 and (b) interferon.

102. A thiazole compound selected from the group consisting of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and 4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole, or a pharmaceutically acceptable salt thereof.

103. A pharmaceutical composition comprising (a) the fused compound of the formula [I] of claim 1 or a pharmaceutically acceptable salt thereof and (b) at least one agent selected from the group consisting of an antiviral agent other than the compound of claim 1, an antiinflammatory agent and an immunostimulant.

104. A pharmaceutical composition comprising (a) the fused compound of the formula [I] of claim 1 or a pharmaceutically acceptable salt thereof and (b) interferon.

105. A method for treating hepatitis C, which comprises administering an effective amount of a fused ring compound of the formula [I] of claim 1 or a pharmaceutically acceptable salt thereof.

106. The method of claim 105, further comprising administering an effective amount of at least one agent selected from the group consisting of an antiviral agent other than the compound of claim 1, an antiinflammatory agent and an immunostimulant.

107. The method of claim 105, further comprising administering an effective amount of interferon.

108. A method for inhibiting hepatitis C virus polymerase, which comprises administering an effective amount of a fused ring compound of the formula [I] of claim 1 or a pharmaceutically acceptable salt thereof.

109. The method of claim 108, further comprising administering an effective amount of at least one agent selected from the group consisting of an antiviral agent other than the compound of claim 1, an antiinflammatory agent and an immunostimulant.

110. The method of claim 108, further comprising administering an effective amount of interferon.